Detection Rates Table

The Detection Rates Table is a compilation of data based on extensive literature review. The detection rates listed reflect the likelihood that Signature Genomic Laboratories' current array CGH technology, the SignatureChip®, will detect a microdeletion or microduplication in patients with phenotypes consistent with each specific clinical condition. These rates are subject to change as additional information is learned about the use of array CGH in clinical diagnostic testing. For most conditions, a negative test result does not exclude a specific clinical diagnosis. The SignatureChip® will not detect sequence alterations or single base pair mutations, or abnormalities in other genes or loci not tested with this technology.

1p36-Xp11.3 |A |B |C |D |E |F |G |H |I |J |K |L |M |N |O |P |R |S |T |U |V |W |X |Subtelomeric |Pericentromeric |Aneuploidy
Condition OMIM# Gene/Locus Location Detection rate for deletion/duplication by microarray Comments Present on SignatureChip Version References
1 2 3 4 WG v1 OS v1 WG v2 OS v2
*Duplication of these regions are associated with a syndrome/clinical phenotype.
Microdeletions or microduplications have been associated with this condition.
Microdeletions or microduplications are rare or not yet associated with this condition.
(FISH)Available only through SignatureFISH™ testing.

Information based on UCSC Genome Browser, March 2006 Assembly.

1p36 Microdeletion *

GeneReviews

Resource

607872  Multiple 1p36~99% have a detectable deletion 
Heilstedt et al. 2003. Am J Hum Genet 72:1200-12. Medline
Heilstedt et al. 2003. Clin Genet 64:310-16. Medline
Yu et al. 2003. Hum Mol Genet 12:2145-52. Medline
 
1q21.1 Microdeletion with susceptibility for thrombocytopenia-absent radius (TAR)

274000  Multiple 1q21.1~99% have a detectable deletionDeletions have also been described in unaffected individuals. 
Klopocki et al. 2007. Am J Hum Genet 80:232-40. Medline
 
1q21.1 Microdeletion with susceptibility to mental retardation, autism, or congenital anomalies *

612474  Multiple 1q21.1~99% have a detectable deletionCandidate genes ACP6 (611471), GJA5 (121013), and GJA8 (600897). Deletions and duplications have also been described in unaffected individuals. 
 
 
 
 
Brunetti-Pierri et al. 2008. Nat Genet 40:1466-71. Medline
Mefford et al. 2008. N Engl J Med 359:1685-99. Medline
 
1q41-q42 Microdeletion

  Multiple 1q41~99% have a detectable deletionCandidate gene DISP1 (607502
 
Shaffer et al. 2007. Genet Med 9:607-16. Medline
Slavotinek et al. 2006. Eur J Hum Genet 14:999-1008. Medline
 
1q44 Microdeletion

  Multiple 1q44~99% have a detectable deletionCandidate gene AKT3 (611223
 
 
 
Hill et al. 2007. Am J Med Genet 143:1692-98. Medline
Van Bever et al. 2005. Am J Med Genet 135:91-95. Medline
Boland et al. 2007. Am J Hum Genet 81:292-303. Medline
 
2p15-p16.1 Microdeletion

  Multiple 2p15-p16.1~99% have a detectable deletion 
 
 
 
 
Racjan-Separovic et al. 2007. J Med Genet 44:269-76. Medline
de Leeuw et al. 2008. J Med Genet 45:122-24. Medline
Chabchoub et al. 2008. J Med Genet 45:189-92. Medline
 
2p21 Microdeletion, homozygous

606407  Multiple 2p21~99% have detectable homozygous deletionsRecessive condition. Phenotypic overlap with Hypotonia-cystinuria syndrome. 
 
 
 
 
 
 
 
Parvari et al. 2001. Am J Hum Genet 69:869-75. Medline
Parvari et al. 2005. Genomics 86:195-211. Medline
 
2q32.2-q33 Microdeletion

119540  Multiple 2q33.1~99% have a detectable deletionCandidate gene SATB2 (119540
 
 
 
 
Van Buggenhout et al. 2005. Eur J Med Genet 48:276-89. Medline
Rosenfeld et al. 2009. PLoS One 4:e6568. Medline
 
3q29 Microdeletion

609425  Multiple 3q29~99% have a detectable deletion 
 
 
 
Willatt et al. 2005. Am J Hum Genet 77:154-60. Medline
 
6p25.3 Microdeletion

  Multiple 6p25.3~99% have a detectable deletionConsiderable phenotypic overlap with Craniocerebello-cardiac dysplasia (220210). 
Descipio et al. 2005. Am J Med Genet 134:3-11. Medline
Lin et al. 2005. Am J Med Genet 136:162-68. Medline
 
6q24.3 Microdeletion

  Multiple 6q24.3~99% have a detectable deletionPhenotype may be limited to deletions of the paternally inherited chromosome. 
 
 
 
 
 
 
Nowaczyk et al. 2008. Am J Med Genet. 146:354-60. Medline
 
7q11.23 Microduplication *

Resource

609757  Multiple 7q11.23~99% have a detectable duplication 
Somerville et al. 2005. N Engl J Med 353:1694-701. Medline
Berg et al. 2007. Genet Med 9:427-41. Medline
Van der Aa et al. 2009. Eur J Med Genet 52(2-3):94-100. Epub 2009 Feb 26. Medline
 
8p23.1 Microdeletion *

  Multiple 8p23.1~99% have a detectable deletionCandidate gene GATA4 (600576). Phenotypic overlap with Congenital diaphragmatic hernia 2 (222400). 
 
Slavotinek et al. 2006. Eur J Hum Genet 14:999-1008. Medline
Pehlivan et al. 1999. Am J Med Genet 83:201-06. Medline
Barber et al. 2008. Eur J Hum Genet 16:18-27. Epub 2007 Oct 17. Medline
 
9q22.32-q22.33 Microdeletion

  Multiple 9q22.33~99% have a detectable deletionCandidate gene TGFBR1 (190181
 
 
 
 
Redon et al. 2006. Eur J Hum Genet 14:759-67. Medline
 
9q34 Microdeletion *

610253  Multiple 9q34.3~99% have a detectable deletionCandidate gene EHMT1 (607001). Rare mutations not detectable by array CGH. 
Yatsenko et al. 2005. J Med Genet 42:328-35. Medline
Kleefstra et al. 2006. Am J Hum Genet 79:370-77. Medline
Ruiter et al. 2007. Clin Genet 72:362-68. Medline
 
10q22.3-q23.31 Microdeletion

  Multiple 10q22.3-q23.31~99% have a detectable deletion 
 
 
 
 
Balciuniene et al. 2007. Am J Hum Genet 80:938-47. Medline
Farrell et al. 1993. J Med Genet 30:248-50. Medline
 
12q14.1-q15 Microdeletion *

  Multiple 12q14.3~99% have a detectable deletionCandidate genes LEMD3 (607844) and GRIP1 (604597). Phenotypic overlap with Buschke-Ollendorff/Osteopoikiloisis (166700). 
 
 
 
 
Menten et al. 2007. J Med Genet 44:264-68. Medline
 
12q24.21-q24.23 Microduplication *

  Multiple 12q24.21-q24.23~99% have a detectable duplication 
 
 
 
 
Doco-Fenzy et al. 2006. Am J Med Genet 140:212-21. Medline
Ruiter et al. 2006. Clin Dysmorphol 15:133-37. Medline
 
14q11.2 Microdeletion

  Multiple 14q11.2~99% have a detectable deletionCandidate genes CHD8 (610528) and SUPT16H (605012). 
 
 
 
 
Zahir et al. 2007. J Med Genet 44:556-61. Medline
 
14q22-q23 Microdeletion

GeneReviews

  Multiple 14q22-q23~99% have a detectable deletion 
 
 
 
 
Nolen et al. 2006. Am J Med Genet 140:1711-18. Medline
 
15q11-q13 Microduplication *

GeneReviews

Resource

608636  Multiple 15q11-q13~99% of interstitial duplications. Precise detection rate of markers depends on size of duplicated regionPhenotype may be primarily associated with duplications of the maternally inherited chromosome. 
Wang et al. 2004. Am J Hum Genet 75:267-81. Medline
Cook et al. 1997. Am J Hum Genet 60:928-34. Medline
 
15q13.3 Microdeletion

612001  Multiple 15q13.3~99% have a detectable deletionCandidate gene CHRNA7 (118511
 
 
 
 
Sharp et al. 2008. Nat Genet 40:322-28. Medline
Miller et al. 2009. J Med Genet 46:242-8. Epub 2008 Sep 19. Medline
Slavotinek 2008. Hum Genet 124:1-17. Epub 2008 May 30. Medline
 
15q24.1-q24.3 Microdeletion

  Multiple 15q24.1-q24.3~99% have a detectable deletion 
 
 
 
 
Sharp et al. 2007. Hum Mol Genet 16:567-72. Medline
Klopocki et al. 2007. Eur J Pediatr 167:903-08. Medline
 
16p11.2-p12.2 Microdeletion *

  Multiple 16p11.2-p12.2~99% have a detectable deletion 
 
 
 
 
Ballif et al. 2007. Nat Genet 39:1071-73. Medline
Finelli et al. 2004. J Med Genet 41:e90. Medline
 
16p11.2 Microdeletion *

GeneReviews

611913  Multiple 16p11.2~99% have a detectable deletionDeletions and duplications have also been described in unaffected individuals. 
 
 
 
 
Ghebranious et al. 2007. Am J Med Genet A 143:1462-71. Medline
Sebat et al. 2007. Science. 316:445-49. Medline
Weiss et al. 2007. N Engl J Med 358:667-75. Medline
 
16p13.1 Microdeletion predisposing to autism and/or mental retardation *

  Multiple 16p13.1~99% have a detectable deletionDeletions and duplications have also been described in unaffected individuals. 
 
 
 
 
Ullmann et al. 2007. Hum Mutat 28:674-82. Medline
Hannes et al. 2009. J Med Genet 46:223-32. Epub 2008 Jun 11. Medline
 
16p13.3 Microdeletion/Severe Rubinstein-Taybi

610543  CREBBP
DNASE1
16p13.3~99% have a detectable deletionPhenotypic overlap with Rubenstein-Taybi (180849). 
Bartsch et al. 2006. Hum Genet 120:179-86. Medline
Bartsch et al. 1999. Eur J Hum Genet 7:748-56. Medline
 
16q11.2-q12.2 Microdeletion

  Multiple 16q11.2-q12.2~99% have a detectable deletionCandidate gene SALL1 (602218) and ZNF423 (604557). Minor phenotypic overlap with Townes-Brocks 1 (107480). 
 
 
 
 
Borozdin et al. 2006. Hum Mutat 27:211-12. Medline
Ballif et al. 2008. Clin Genet 74:469–75. Medline
 
17q21.3 Microdeletion *

Resource

610443  Multiple 17q21.3~99% have a detectable deletionCandidate gene MAPT (157140
 
 
 
 
Shaw-Smith et al. 2006. Nat Genet 38:1032-37. Medline
Sharp et al. 2006. Nat Genet 38:1038-42. Medline
Kirkhhoff et al. 2007. Eur J Med Genet 50:256-63. Medline
 
22q11.2 Distal microdeletion *

611867  Multiple 22q11.2~99% have a detectable deletion 
 
 
 
Ben-Shachar et al. 2008. Am J Hum Genet 82:214-21. Medline
Rauch et al. 2005. J Med Genet 42:871-76. Medline
 
22q11.21 Microduplication *

GeneReviews

608363  Multiple 22q11.21~99% have a detectable duplicationDuplications have also been described in unaffected individuals. Candidate gene TBX1 (602054
Ensenauer et al. 2003. Am J Hum Genet 73:1027-40. Medline
Alberti et al. 2007. Clin Genet 71:177-82. Medline
Wentzel et al. 2008. Eur J Med Genet 51:501-10. Medline
Torres-Juan et al. 2007. Eur J Hum Genet 15:658-63. Medline
 
22q13.3 Microdeletion *

GeneReviews

606232  Multiple 22q13.3~99% have a detectable deletionCandidate genes ARSA (607574) and SHANK3 (606230). 
 
 
 
Anderlid et al. 2002. Hum Genet 110:439-43. Medline
Luciani et al. 2003. J Med Genet 40:690-96. Medline
Phelan et al. 2001. Am J Med Genet 101:91-99. Medline
Okamoto et al. 2007. Am J Med Genet 143:2804-09. Medline
 
Xp11.22-linked mental retardation *

  Multiple Xp11.22Precise detection rate unknownCandidate gene HSD17B10 (300256) and HUWE1 (300697). Rare mutations in either gene not detectable by array CGH. 
 
 
 
 
 
 
Froyen et al. 2008. Am J Hum Genet 82:432-43. Medline
 
Xp11.3 Microdeletion

Resource

300578  Multiple Xp11.3~99% have a detectable deletionCandidate genes RP2 (312600) and ZNF674 (300573). 
 
 
 
 
Zhang et al. 2006. Am J Med Genet 140:349-57. Medline
Lugtenberg et al. 2006. Am J Hum Genet 78:265-78. Medline
 
Xp11.4-p21.2 Contiguous gene deletion

  Multiple Xp11.1-p21.2~99% have a detectable deletion 
Jin et al. 2000. Eur J Hum Genet 8:87-97. Medline
Bertelson et al. 1988. Am J Hum Genet 42:703-11. Medline
Wong et al. 2008. Clin Chem. 54:1141-8. Epub 2008 May 16. Medline
 
Adrenal hypoplasia congenita (AHC)

GeneReviews

300200  NR0B1
Xp21.2~18% have a detectable deletion in isolated AHC; ~ 99% have a detectable deletion in AHC/GKD or AHC/GKD/DMD~53% have mutations not detectable by array CGH 
Guo et al. 1995. JAMA 274:324-30. Medline
Peter et al. 1998. J Clin Endocrin Metab 83: 2666-74. Medline
 
Adult-onset autosomal dominant leukodystrophy (ADLD) * (FISH)

169500  LMNB1
5q23.2Precise detection rate unknownAvailable as FISH test only. Not routinely tested by the SignatureChip® This test is available as a stand-alone FISH test only.
Padiath et al. 2006. Nat Genet 38:1114-23. Medline
 
Alagille

GeneReviews

118450  JAG1
20p12.23-7% have a detectable deletionMajority have mutations not detectable by array CGH 
Krantz et al. 1998. Am J Hum Genet 62:1361-69. Medline
Spinner et al. 2001. Hum Mutat 17:18-33. Medline
 
Albright hereditary osteodystrophy-like/Brachydactyly-MR

GeneReviews

Resource

600430  Multiple 2q37.3Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
Aldred et al. 2004. J Med Genet 41:433-39. Medline
Phelan et al. 1995. Am J Med Genet 58:1-7. Medline
Shrimpton et al. 2004. Clin Genet 66:537-44. Medline
Wilson et al. 1995. Am J Hum Genet 56:400-07. Medline
 
Alpha thalassemia mental retardation (ATR-16)

141750  Multiple 16p13.3~99% have a detectable deletionDeletion HBA1 (141800) and HBA2 (141850) responsible for alpha-thalassemia phenotype. 
 
 
 
Wilkie et al. 1990. Am J Hum Genet 46:1112-26. Medline
Harteveld et al. 2007. Hum Genet. 122:283-92. Medline
 
Alzheimer disease, early onset with cerebral amyloid angiopathy * (FISH)

GeneReviews

104300  APP
21q21.3~8% have a detectable duplicationAvailable as FISH test only. ~16% have mutations not detectable by FISH. Not routinely tested by the SignatureChip® This test is available as a stand-alone FISH test only.
Rovelet-Lecrux et al. 2006. Nat Genet 38:24-26. Medline
Raux et al. 2005. J Med Genet 42:793-95. Medline
 
Androgen insensitivity

GeneReviews

300068  AR
Xq12Deletions uncommon~50% have mutations not detectable by array CGH 
 
 
 
 
 
 
Davies et al. 1997. J Med Genet 34:158-60. Medline
Jakubiczka et al. 1997. Hum Mutat 9:57-61. Medline
Quigley et al. 1992. J Clin Endocrin & Metab 74:927-33. Medline
 
Angelman

GeneReviews

105830  UBE3A
15q11.2~70% have a detectable deletion~30% have either paternal UPD or mutations not detectable by array CGH 
Magenis et al. 1987. Am J Med Genet 28:829-38. Medline
Zacowski et al. 1993. Am J Med Genet 46:7-11. Medline
 
Aniridia II

GeneReviews

106210  PAX6
11p13Rare deletions unless associated with contiguous gene syndromeMajority have mutations not detectable by array CGH 
Crolla et al. 2002. Am J Hum Genet 71:1138-49. Medline
Gronskov et al. 2001. Hum Genet 109:11-18. Medline
 
Atrial septal defect (ASD) with atrioventricular conduction defects

Resource

108900  NKX2-5
5q35.2Deletions uncommon10-27% have mutations not detectable by array CGH 
 
 
 
 
Baekvad-Hansen et al. 2006. Am J Med Genet 140:427-33. Medline
Sarkozy et al. 2005 J Med Genet 42:e16. Medline
Benson et al. 1999. J Clin Invest 104:1567-73. Medline
 
Bannayan-Riley-Ruvalcaba (BRRS)

Signature Summary on PTEN Hamartoma Tumor Syndrome

GeneReviews

153480  PTEN
10q23.312-11% have a detectable deletion~60% have mutations not detectable by array CGH. Allelic with Cowden (158350)/Macrocephaly/autism (605309)/Proteus/Proteus-like (176920). 
 
 
 
 
Marsh et al. 1998. Hum Mol Genet 7:507-15. Medline
Marsh et al. 1999. Hum Mol Genet 8:1461-72. Medline
Zhou et al. 2003. Am J Hum Genet 73:404-11. Medline
 
Bartter, antenatal 1

Resource

601678  SLC12A1
15q21.1Precise detection rate unknownRecessive condition. Majority of cases have at least one mutation not detectable by array CGH 
 
 
 
 
Vargas-Poussou et al. 1998. Am J Hum Genet 62:1332-40. Medline
Simon et al. 1996. Nat Genet 13:183-88. Medline
 
Bartter, antenatal 2

Resource

241200  KCNJ1
11q24.3Precise detection rate unknownRecessive condition. Majority of cases have at least one mutation not detectable by array CGH 
 
 
 
 
Károlyi et al. 1997. Hum Mol Genet 6:17-26. Medline
Feldmann et al. 1998. J Am Soc Nephrol 9:2357-59. Medline
Jeck et al. 2001. Kidney Int 59:1803-11. Medline
 
Bartter 3 (classic)

Resource

607364  CLCNKB
1p36.13Precise detection rate unknownRecessive condition. Majority of cases have at least one mutation not detectable by array CGH 
 
 
 
 
Konrad et al. 2000. J Am Soc Nephrol 11:1449-59. Medline
Simon et al. 1997. Nat Genet 17:171-78. Medline
 
Bartter 4 (infantile with sensorineural deafness)

Resource

602522  BSND
or
CLCNKA and CLCNKB
1p32.3 1p36.13UnknownRecessive condition. Majority have mutations not detectable by array CGH 
 
 
 
 
Birkenhäger et al. 2001. Nat Genet 29:310-14. Medline
Schlingmann et al. 2004. NEJM 350:1314-19. Medline
 
Basal cell nevus/Gorlin-Goltz

109400  PTCH1
9q22.32Deletions uncommonAllelic with Holoprosencephaly 7 (610828). 
Boonen et al. 2005. Am J Med Genet 132:324-28. Medline
 
Beckwith-Wiedemann, IGF2-related *

130650  IGF2
11p15.5Duplications uncommonMajority have paternal isodisomy or mutations not detectable by array CGH 
Henry et al. 1993. Eur J Hum Genet 1:19-29. Medline
Li et al. 1998. Am J Med Genet 79:253-59. Medline
Slavotinek et al. 1997. J Med Genet 34:819-26. Medline
 
Beckwith-Wiedemann, KCNQ1OT1-related

130650  KCNQ1OT1
11p15.5Rare deletionsMajority have paternal isodisomy or mutations not detectable by array CGH 
 
 
 
 
Niemitz et al. 2004. Am J Hum Genet 75:844-49. Medline
 
Benign neonatal epilepsy

Resource

121200  KCNQ2
20q13.33~3.3% have a detectable deletion~37% have mutations not detectable by array CGH 
 
 
 
 
 
 
Heron et al. 2007. J Med Genet 44:791-96. Medline
Singh et al. 2003. Brain 126:2726-37. Medline
 
Bilateral frontoparietal polymicrogyria (BFPP)

GeneReviews

606854  GPR56
16q13UnknownRecessive condition. Majority of cases have at least one mutation not detectable by array CGH 
 
 
 
 
Piao et al. 2004. Science 303:2033-36. Medline
 
Blepharophimosis, ptosis epicanthus inversus (BPE)

GeneReviews

110100  FOXL2
3q22.3Precise detection rate unknown 
 
 
 
Crisponi et al. 2001. Nat Genet 27:159-66. Medline
 
Boston-type craniosynostosis *

Resource

604757  MSX2
5q35.2Precise detection rate unknownAllelic with Parietal foramina 1 (168500
 
 
 
 
Bernardini et al. 2007. Am J Med Genet 143:2937-43. Medline
Wang et al. 2007. Am J Med Genet 143:2931-36. Medline
Jabs et al. 1993. Cell 75:443-50. Medline
 
Branchio-oto-renal (BOR)/Melnick-Fraser

GeneReviews

113650  EYA1
8q13.37-11% have a detectable deletion~40% have mutations not detectable by array CGH. Allelic with Oto-facio-cervical (166780). 
 
 
 
Abdelhak et al. 1997. Hum Mol Genet 6:2247-55. Medline
Chang et al. 2004. Hum Mutat 23:582-89. Medline
 
Buschke-Ollendorff

166700  LEMD3
12q14.3UnknownPhenotypic overlap with 12q14.1-q15 Microdeletion 
 
 
 
 
Hellemans et al. 2004. Nat Genet 36:1213-18. Medline
 
Campomelic dysplasia (CMPD)

Resource

114290  SOX9
17q24.3Deletions uncommonMajority have mutations not detectable by array CGH 
 
 
 
Olney et al. 1999. Am J Med Genet 84:20-24. Medline
 
Cat-eye *

Resource

115470  Multiple 22q11.1Precise detection rate unknownThe supernumary marker chromosome is detectable by array CGH 
Bartsch et al. 2005. Eur J Hum Genet 13:592-98. Medline
Johnson et al. 1999. Genomics 57:306-309. Medline
Rosias et al. 2001. Genet Couns 12:273-82. Medline
 
Cerebellar hypoplasia, VLDLR-related/Hutterite dysequilibrium

GeneReviews

224050  VLDLR
9p24.2Rare deletions in most populations; ~99% have homozygous deletions in Hutterite populationRecessive condition. Rare mutations are not detectable by array CGH. 
 
 
 
 
 
 
Boycott et al. 2005. Am J Hum Genet 77:477-83. Medline
Ozcelik et al. 2008. Proc Natl Acad Sci U S A 105:4232-36. Medline
 
Cerebral cavernous malformations, type 1 (CCM1)

GeneReviews

116860  KRIT1
7q21.2Precise detection rate unknown~40% have mutations not detectable by array CGH 
 
 
 
 
Gaetzner et al. 2007. Neurosurg Rev 30:155-59. Medline
Asmus et al. 2007. Brain 130:2736-45. Medline
Liquori et al. 2007. Am J Hum Genet 80:69-75. Medline
 
Cerebral cavernous malformations, type 2 (CCM2)

GeneReviews

603284  CCM2
7p13~13% have a detectable deletion~38% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Liquori et al. 2007. Am J Hum Genet 80:69-75. Medline
 
Cerebral cavernous malformations, type 3 (CCM3)

GeneReviews

603285  PDCD10
3q26.1~1.3% have a detectable deletion6-9% have mutations not detectable by array CGH 
 
 
 
 
 
 
Liquori et al. 2007. Am J Hum Genet 80:69-75. Medline
Bergametti et al. 2005. Am J Hum Genet 76:42-51. Medline
 
CHARGE

Resource

214800  CHD7
8q12.2~10% have a detectable deletionMajority have mutations not detectable by array CGH 
 
Vissers et al. 2004. Nat Genet 36:955-57. Medline
 
Choroideremia

GeneReviews

303100  CHM
Xq21.2~3% have a detectable deletion57-91% have mutations not detectable by array CGH 
 
 
 
 
 
 
McTaggart et al. 2002. Hum Mutat 20:189-96. Medline
van den Hurk et al. 2003. Hum Genet 113:268-75. Medline
 
Cleidocranial dysplasia (CCD)

GeneReviews

119600  RUNX2
6p12.3Deletions uncommonMajority have mutations not detectable by array CGH 
 
 
 
Mundlos et al. 1997. Cell 89:773-79. Medline
Otto et al. 2002. Hum Mutat 19:209-16. Medline
 
Congenital deafness with inner ear agenesis, microtia, & microdontia

Resource

610706  FGF3
11q13.3Precise detection rate unknownRecessive condition. Allelic with Oto-dental syndrome (166750
 
 
 
 
Tekin et al. 2007. Am J Hum Genet 80:338-44. Medline
 
Congenital diaphragmatic hernia (CDH)

142340  CHD2
NR2F2
15q26.1 15q26.21-2% have a detectable deletion 
 
 
 
Klaasens et al. 2005. Am J Hum Genet 76:877-82. Medline
Schlembach et al. 2001. Prenat Diagn 21:289-92. Medline
 
Congenital diaphragmatic hernia 2 (CDH2) *

GeneReviews

222400  Candidate GATA4 (600576)
8p23.1~3% have a detectable deletionMajority of reported deletions are detectable by array CGH. Phenotypic overlap with 8p23.1 Microdeletion. GATA4 candidate gene (600576). 
 
 
 
 
Slavotinek et al. 2006. Eur J Hum Genet 14:999-1008. Medline
Barber et al. 2008. Eur J Hum Genet 16:18-27. Epub 2007 Oct 17. Medline
Slavotinek et al. 2005. J Med Genet 42:730-36. Medline
 
Cornelia de Lange

GeneReviews

122470  NIPBL
5p13.2Rare deletions~47% have mutations not detectable by array CGH 
 
DeScipio et al. 2005. Am J Med Genet 137:276-82. Medline
Gillis et al. 2004. Am J Hum Genet 75:610-23. Medline
Krantz et al. 2004. Nat Genet 36:631-35. Medline
 
Cowden

158350  PTEN
10q23.31~1% have a detectable deletion~80% have mutations not detectable by array CGH. Allelic with Bannayan-Riley-Ruvalcaba (153480)/Macrocephaly/autism (605309)/Proteus/Proteus-like (176920). 
 
 
 
 
Marsh et al. 1998. Hum Mol Genet 7:507-15. Medline
Zhou et al. 2003. Am J Hum Genet 73:404-11. Medline
 
Craniofrontonasal

Resource

304110  EFNB1
Xq13.1Precise detection rate unknown~87% have mutations not detectable by array CGH 
 
 
 
 
 
 
Twigg et al. 2004. Proc Natl Acad Sci U S A 101:8652-57. Medline
Wieland et al. 2005. Hum Mutat 26:113-18. Medline
Wieland et al. 2007. Clin Genet 72:506-16. Medline
 
Cri-du-Chat

123450  Multiple 5p15.2~ 99% have a detectable deletion 
Church et al. 1997. Genome Res 7:787-801. Medline
Mainardi et al. 2001. J Med Genet. 38:151-58. Medline
Zhang et al. 2005. Am J Hum Genet 76:312-26. Medline
 
Currarino

Resource

176450  MNX1
7q36.32-3% have a detectable deletion26-75% have mutations not detectable by array CGH 
 
 
 
Hagan et al. 2000. Am J Hum Genet 66:1504-15. Medline
Belloni et al. 2000. Am J Hum Genet 66:312-19. Medline
 
Dandy-Walker malformation (DWM)

Resource

Resource

220200  ZIC1
ZIC4
3q24Deletions uncommon 
 
 
 
Grinberg et al. 2004. Nat Genet 36:1053-55. Medline
 
DiGeorge/Velocardiofacial (VCF)

GeneReviews

188400  HIRA
TBX1
22q11.21>95% have a detectable deletion 
Mantripragada et al. 2004. Int J Mol Med 13:273-79. Medline
Shaikh et al. 2000. Hum Mol Genet. 9:489-501. Medline
Yagi et al. 2003. Lancet 362:1366-73. Medline
 
DiGeorge 2

Resource

601362  Multiple 10p14<1% have a detectable deletion 
Berend et al. 2000. Am J Med Genet 91:313-17. Medline
Van Esch et al. 1999. Clin Genet 55:269-76. Medline
 
Dosage sensitive sex reversal *

Resource

300018  NR0B1
Xp21.2Precise detection rate unknown 
Bardoni et al. 1994. Nat Genet 7:497-501. Medline
Sanlaville et al. 2004. Am J Med Genet 128:325-30. Medline
 
Down syndrome critical region (DSCR) *

Resource

602917  Multiple 21q22.13Precise detection rate unknownMajority of reported duplications are detectable by array CGH 
 
 
 
Korenberg et al. 1990. Am J Hum Genet 47:236-46. Medline
Delabar et al. 1993. Eur J Hum Genet 1:114-24. Medline
Barlow et al. 2001. Genet Med 3:91-101. Medline
Ronan et al. 2007. J Med Genet 44:448-51. Medline
 
Familial adenomatous polyposis (FAP)/Gardner/MR

GeneReviews

175100  APC
5q22.2>98% have a detectable deletionMajority of isolated FAP cases have mutations not detectable by array CGH 
 
 
 
Pilarski et al. 1999. Am J Med Genet 86:321-24. Medline
Raedle et al. 2001. Am J Gastroent 96:3016-20. Medline
 
Familial hypocalciuric hypercalcemia 1 (HHC1)

Resource

145980  CASR
3q21.1Unknown~40-67% have mutations not detectable by array CGH. Allelic with Neonatal severe primary hypoparathyroidism (239200). 
 
 
 
 
Chou et al. 1995. Am J Hum Genet 56:1075-79. Medline
Pearce et al. 1995. J Clin Invest 96:2683-92. Medline
 
Feingold

Resource

164280  MYCN
2p24.3~4% have a detectable deletion~63% have deletions not detectable by array CGH 
 
 
 
 
Celli et al. 2000. Am J Hum Genet 66:436-44. Medline
van Bokhoven et al. 2005. Nat Genet 37:465-67. Medline
 
FG 5 *

Resource

300581  MID2
Xq22.3Rare duplicationsMajority of reported duplications are detectable by array CGH 
 
 
 
 
Jehee et al. 2005. Am J Med Genet 139:221-26. Medline
 
FMR1 microdeletion

GeneReviews

300624  FMR1
Xq27.3<1% of individuals with Fragile X have a detectable deletion>99% of individuals with Fragile X have CGG triplet expansions or other mutations not detectable by by array CGH 
 
 
 
 
Quan et al. 1995. Am J Hum Genet 56:1042-51. Medline
Hammond et al. 1997. Am J Med Genet 72:430-4. Medline
 
Focal dermal hypoplasia/Goltz

GeneReviews

305600  PORCN
Xp11.235.6-20% have a detectable deletion70-72% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Wang et al. 2007. Nat Genet 39:836-38. Medline
Grzeschik et al. 2007. Nat Genet 39:833-35. Medline
 
Fryns

GeneReviews

229850  Candidate DISP1 (607502)
1q41Precise detection rate unknownMajority of reported deletions are detectable by by array CGH 
 
Shaffer et al. 2007. Genet Med 9:607-16. Medline
Slavotinek et al. 2006. Eur J Hum Genet 14:999-1008. Medline
 
Generalized epilepsy with febrile seizures plus 2 (GEFS+2)

604233  SCN1A
2q24.4Unknown~6% have mutations not detectable by array CGH. Allelic with Severe myoclonic epilepsy of infancy (607208). 
 
 
 
 
Wallace et al. 2001. Am J Hum Genet 68:859-65. Medline
 
Gitelman

Resource

263800  SLC12A3
16q13Precise detection rate unknownRecessive condition. Majority have at least one mutation not detectable by array CGH 
 
 
 
 
Mastroianni et al. 1996. Am J Hum Genet 59:1019-26. Medline
Syrén et al. 2002. Hum Mutat 20:78. Medline
 
Glycerol kinase deficiency (GKD)

Resource

300474  GK
Xp21.2Deletions uncommonMajority have mutations not detectable by array CGH 
Sargent et al. 2000 J Med Genet 37:434-41. Medline
 
Greig cephalopolysyndactyly

GeneReviews

175700  GLI3
7p14.1~30% have a detectable deletion 
Johnston et al. 2003. Am J Med Genet 123:236-42. Medline
 
Hemophilia A

GeneReviews

306700  F8
Xq28~2.0% have a detectable deletion~93% have mutations not detectable by array CGH 
 
 
 
 
 
 
Higuchi et al. 1989. Blood 74:1045-51. Medline
Casula et al. 1990. Blood 75:662-70. Medline
Higuchi et al. 1991. Proc Natl Acad Sci USA 88:7405-409. Medline
Sanna et al. 2008. Haemophilia 14:796-803. Medline
 
Hemophilia B

GeneReviews

306900  F9
Xq27.1~2.0% have a detectable deletion~97% have mutations not detectable by array CGH 
 
 
 
 
 
 
Ketterling et al. 1994. Am J Hum Genet 54:201-13. Medline
Belvini et al. 2005. Haematologica 90:635-42. Medline
 
Hereditary hemorrhagic telangiectasia, type 2

GeneReviews

600376  ACVRL1
12q13.13~1.7% have a detectable deletion~40% have mutations not detectable by array CGH 
 
 
 
 
Lesca et al. 2004. Hum Mutat 23:289-99. Medline
Shoukier et al. 2008. Clin Genet. 73:320-30. Medline
 
Holoprosencephaly

SignatureChip® Detection Rates for Holoprosencephaly

25-50% of cases with holoprosencephaly (HPE) have abnormal karyotypes, the vast majority of which are detectable by SignatureChip®.

15-20% of HPE cases with normal chromosomes will have sequence mutations in SHH, ZIC2, SIX3, or TGIF. Sequence mutations are not detectable by array CGH. A negative array CGH test result does not exclude the possibility that one or more of these genes may play a role in the subject's phenotype.

4.7% of chromosomally normal and mutation-analysis normal HPE cases have microdeletions in SHH, ZIC2, SIX3 or TGIF (Bendavid et al. 2006. Hum Genet 119:1-8. Medline). The majority of reported microdeletions are detectable by SignatureChip®.

Holoprosencephaly 1

236100  TRAPPC10
21q22.3Unknown 
Muenke et al. 1995. Am J Hum Genet 57:1074-9. Medline
Nagamine et al. 1997. Biochem Biophys Res Commun 235:185-90. Medline
 
Holoprosencephaly 2

157170  SIX3
2p21~1% have a detectable deletion~4% have mutations not detectable by array CGH 
Bendavid et al. 2006. Hum Genet 119:1-8. Medline
Dubourg et al. 2004. Hum Mutat 24:43-51. Medline
Ming et al. 2002. Am J Hum Genet 71:1017-32. Medline
 
Holoprosencephaly 3

142945  SHH
7q36.31-2% have a detectable deletion6-8% have mutations not detectable by array CGH 
Bendavid et al. 2006. Hum Genet 119:1-8. Medline
Ming et al. 2002. Am J Hum Genet 71:1017-32. Medline
Nanni et al. 1999. Hum Mol Genet 8:2479-88. Medline
 
Holoprosencephaly 4

142946  TGIF1
18p11.31<1% have a detectable deletion~1% have mutations not detectable by array CGH 
Bendavid et al. 2006. Hum Genet 119:1-8. Medline
Dubourg et al. 2004. Hum Mutat 24:43-51. Medline
Ming et al. 2002. Am J Hum Genet 71:1017-32. Medline
Gripp et al. 2000. Nat Genet 25:205-208. Medline
 
Holoprosencephaly 5

609637  ZIC2
13q32.3<1% have a detectable deletion~3% have mutations not detectable by array CGH 
Bendavid et al. 2006. Hum Genet 119:1-8. Medline
Dubourg et al. 2004. Hum Mutat 24:43-51. Medline
Brown et al. 2001. Hum Molec Genet 10:791-96. Medline
 
Holoprosencephaly 6

605934  Multiple 2q37.1-q37.3Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
Lehman et al. 2001. Am J Med Genet 100:179-81. Medline
 
Holoprosencephaly 7

610828  PTCH1
9q22.32UnknownAllelic with Basal cell nevus/Gorlin-Goltz (109400
Ming et al. 2002. Hum Genet 110:297-301. Medline
 
Holoprosencephaly 8

609408  Multiple 14q13.1-q13.2Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
 
 
 
 
Kamnasaran et al. 2005. Genomics 85:608-21. Medline
 
Holoprosencephaly and preaxial polydactyly *

Signature Summary on Holoprosencephaly

GeneReviews

605651  FBXW11
5q35.1Precise detection rate unknownMajority of reported duplications are detectable by array CGH 
 
 
 
 
Koolen et al. 2006. J Hum Genet 51:721-26. Medline
 
Holt-Oram *

142900  TBX5
12q24.1Rare deletions30-35% have mutations not detectable by array CGH 
 
 
 
 
Doco-Fenzy et al. 2006. Am J Med Genet 140:212-21. Medline
Borozdin et al. 2006. Am J Med Genet 140:1880-86. Medline
Brassington et al. 2003. Am J Hum Genet 73:74-85. Medline
Cross et al. 2000. J Med Genet 37:785-87. Medline
 
Hypoparathyroidism, sensorineural deafness, renal disease (HDR)

Resource

146255  GATA3
10p14~40% have a detectable deletion10-20% have mutations not detectable by array CGH 
 
 
 
Muroya et al. 2001. J Med Genet 38:374-80. Medline
Van Esch et al. 2000. Nature 406:419-22. Medline
 
Hypotonia-cystinuria

606407  SLC3A1
PREPL
2p21~99% have detectable homozygous deletionsRecessive condition. Phenotypic overlap with 2p21 microdeletion syndrome 
 
 
 
 
 
 
 
Jaeken et al. 2006. Am J Hum Genet 78:38-51. Medline
 
Infantile hyperinsulinism with enteropathy & deafness

606528  USH1C
ABCC8
11p15.1Precise detection rate unknownRecessive condition. Phenotypic overlap with Usher syndrome 1C (276904) and Familial hyperinsulinemic hypoglycemia 1 (256450). 
 
 
 
 
 
 
Bitner-Glindzicz et al. 2000. Nat Genet 26:56-60. Medline
Hussain et al. 2004. J Pediatr Endocrinol Metab 17:1613-21 Medline
 
Infantile spasms, MAGI2-related

606382  MAGI2
7q21.11Precise detection rate unknown 
 
 
 
 
 
 
Marshall et al. 2008. Am J Hum Genet 83:106-11. Medline
 
Jacobsen/11q terminal deletion disorder

147791  Multiple 11q23 -11qterPrecise detection rate unknownMajority of reported deletions are detectable by array CGH 
De Pater et al. 1997. Genet Couns 8:335-39. Medline
Grossfeld et al. 2004. Am J Med Genet 129:51-61. Medline
Tunnacliffe et al. 1999. Genome Res 9:44-52. Medline
 
Joubert 3

608629  AHI1
6q23.3UnknownRecessive condition. ~11% have at least one mutation not detectable by array CGH 
 
 
 
 
Parisi et al. 2006. J Med Genet 43:334-39. Medline
 
Joubert 4

GeneReviews

609583  NPHP1
2q13Precise detection rate unknownRecessive condition. Allelic with Nephronopthisis 1 (256100). 
Parisi et al. 2004. Am J Hum Genet 75:82-91. Medline
 
Joubert 5

GeneReviews

610188  CEP290
12q21.32UnknownRecessive condition. ~7% have at least one mutation not detectable by array CGH. Allelic with Leber Congenital Amaurosis X (611755)/Meckel 4 (611134)/Senior-Loken 6 (610189). 
 
 
 
 
Helou et al. 2007. J Med Genet 44:657-63. Medline
 
Juvenile polyposis (JPS), BMPR1A-related

174900  BMPR1A
10q23.21-7% have a detectable deletion11-21% have mutations not detectable by array CGH 
 
 
 
 
Sweet et al. 2005. JAMA 19:2465-73. Medline
Pyatt et al. 2006. J Molec Diagn 8:84-88. Medline
Aretz et al. 2007. J Med Genet. 44:702-709. Medline
Howe et al. 2004. J Med Genet 41:484-91. Medline
 
Juvenile polyposis (JPS), SMAD4-related

174900  SMAD4
18q21.24-6% have a detectable deletion19-22% have mutations not detectable by array CGH 
 
 
 
 
Pyatt et al. 2006. J Molec Diagn 8:84-88. Medline
Aretz et al. 2007. J Med Genet. 44:702-709. Medline
Howe et al. 2004. J Med Genet 41:484-91. Medline
van Hattem et al. 2008. Gut 57:623-27. Medline
 
Kallmann 1

Resource

308700  KAL1
Xp22.3110-12% have a detectable deletion 
Ballabio et al. 1986. Hum Genet 72:237-40. Medline
Hardelin et al. 1993. J Clin Endocrinol Metab 76:827-31. Medline
Sato et al. 2004. J Clin Endocrinol Metab 89:1079-88. Medline
 
Langer-Giedion

Resource

150230  TRPS1
EXT1
8q23.3 8q24.11~75% have a detectable deletion 
Ahn et al. 1995. Nat Genet 11:137-43. Medline
Ludecke et al. 1995. Hum Mol Genet 4:31-36. Medline
Nardmann et al. 1997. Hum Genet 99:638-43. Medline
 
Langer mesomelic dysplasia (LMD)

Resource

249700  SHOX
Xpter-Xp22.3 & Ypter-Yp11.32Precise detection rate unknownRecessive condition. Many reported deletions are detectable by array CGH. Allelic with X-linked idiopathic short stature (300582)/Leri-Weill dyschondrosteosis (127300). 
Thomas et al. 2004. Am J Med Genet 128:179-84. Medline
Robertson et al. 2000. J Med Genet 37:959-64. Medline
 
Leber congenital amaurosis X (LCAX)

GeneReviews

611755  CEP290
12q21.32UnknownRecessive condition. ~21% have at least one mutation not detectable by array CGH. Allelic with Joubert 5 (610188)/Meckel 4(611134)/Senior-Loken 6(610189). 
 
 
 
 
den Hollander et al. 2006. Am J Hum Genet 79:556-61. Medline
 
Leri-Weill dyschondrosteosis (LWD)

GeneReviews

127300  SHOX
Xpter-Xp22.3 & Ypter-Yp11.3234-41% have detectable deletions~23% have mutations not detectable by array CGH. Allelic with X-linked idiopathic short stature (300582)/Langer mesomelic dysplasia (249700). 
Huber et al. 2006. J Med Genet 43:735-39. Medline
Benito-Sans et al. 2006. Am J Hum Genet 79:409-14. Medline
Schneider et al. 2005. Am J Hum Genet 77:89-96. Medline
 
Li-Fraumeni 1 (LFS)

151623  TP53
17p13.1Deletions uncommon71-79% have mutations not detectable by array CGH 
 
 
 
 
Bougeard et al. 2003. Oncogene 22:840-46. Medline
Varley et al. 2003. Hum Mutat 21:313-20. Medline
Varley et al. 1997. Cancer Res 57:3245-52. Medline
Bougeard et al. 2008. J Med Genet. 45:535-38. Medline
Adam et al. 2009. J Pediatr 154:143-46. Medline
 
Lissencephaly 1

GeneReviews

607432  PAFAH1B1
17p13.3>13% have detectable deletions 
Pilz et al. 1998. Genet Med 1:29-33. Medline
 
Lissencephaly with cerebellar hypoplasia

257320  RELN
7q22.1Unknown 
 
 
 
 
Hong et al. 2000. Nat Genet 26:93-96. Medline
 
Loeys-Dietz (LDS), TGFBR1-related

609192  TGFBR1
9q22.33Unknown~25% have mutations not detectable by array CGH 
 
 
 
 
Loeys et al. 2005. Nat Genet 37:275-81. Medline
Loeys et al. 2006. NEJM 355:788-98. Medline
 
Loeys-Dietz (LDS), TGFBR2-related

610168  TGFBR2
3p24.1Unknown~56% have mutations not detectable by array CGH. Allelic with Marfan 2 (154705). 
 
 
 
 
Loeys et al. 2006. NEJM 355:788-98. Medline
 
Lowe

309000  OCRL
Xq25Large deletions uncommonMajority have mutations not detectable by array CGH 
 
 
 
 
Addis et al. 2007. Eur J Med Genet 50:79-84. Medline
Lin et al. 1997. Am J Hum Genet 60:1384-88. Medline
 
Macrocephaly/autism

Signature Summary on PTEN Hamartoma Tumor Syndrome

605309  PTEN
10q23.31Unknown~4% have mutations not detectable by array CGH. Allelic with Bannayan-Riley-Ruvalcaba (153480)/Cowden (158350)/Proteus/Proteus-like (176920). 
 
 
 
 
Butler et al. 2005. J Med Genet 42:318-21. Medline
Buxbaum et al. 2007. Am J Med Genet B 144:484-91. Medline
 
Marfan 1 (MFS1)

154700  FBN1
15q21.1<1% have a detectable deletion60-93% have mutations not detectable by array CGH 
 
 
 
 
Mátyás et al. 2007. Hum Genet 122:23-32. Medline
Halliday et al. 2002. J Med Genet 39:589-93. Medline
Loeys et al. 2004. Hum Mutat 24:140-46. Medline
 
Marfan 2 (MFS2)

610380  TGFBR2
3p24.1Unknown~12% have mutations not detectable by array CGH. Allelic with Loeys-Dietz (609192). 
 
 
 
 
Singh et al. 2006. Hum Mutat 27:770-77. Medline
 
McLeod

GeneReviews

314850  XK
Xp21.15.8-17% have a detectable deletion~82% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Bertelson et al. 1988. Am J Hum Genet 42:703-11. Medline
Danek et al. 2001. Ann Neurol. 50:755-64. Medline
 
Meckel 4

Resource

611134  CEP290
12q21.32UnknownRecessive condition. ~10% have at least one mutation not detectable by array CGH. Allelic with Joubert 5 (610188)/Leber congenital amaurosis X (611755)/Senior-Loken 6 (610189). 
 
 
 
 
Baala et al. 2007. Am J Hum Genet 81:170-79. Medline
 
Menkes (MNK)

GeneReviews

309400  ATP7A
Xq21.1~1% have a detectable deletion~79% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Tümer et al. 2003. Hum Mutat 22:457-64. Medline
 
Microphthalmia 3

206900  SOX2
3q26.33~2% have a detectable deletion~8% have mutations not detectable by array CGH 
 
 
 
 
Bakrania et al. 2007. Br J Ophthalmol 91:1471-76. Medline
 
Microphthalmia 7 with linear skin defects

Resource

309801  Multiple Xp22.2Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
Kayserili et al. 2001. J Med Genet 38:411-17. Medline
Zvulunov et al. 1998. Br J Dermatol 138:1046-52. Medline
Prakash et al. 2002. Hum Mol Genet 11:3237-48. Medline
 
Miller-Dieker

GeneReviews

247200  PAFAH1B1
17p13.385-90% have a detectable deletion 
Pilz et al. 1998. Genet Med 1:29-33. Medline
Cardoso et al. 2003. Am J Hum Genet 72:918-30. Medline
Dobyns et al. 1991. Am J Hum Genet 48:584-94. Medline
Ledbetter et al. 1992. Am J Hum Genet 50:182-89. Medline
 
Mohr-Tranebjaerg

GeneReviews

304700  TIMM8A
Xq22.1Rare deletions unless associated with contiguous gene deletion syndromeMajority have mutations not detectable by array CGH. Contiguous gene deletion syndrome also involves X-linked agammaglobulinemia (300300). 
 
 
 
 
Šedivá et al. 2007. J Clin Immunol 27:640-46. Medline
 
Mowat-Wilson *

235730  ZEB2
2q22.3~15-21% have a detectable deletion~21-28% have mutations not detectable by array CGH 
 
 
 
 
Ishihara et al. 2004. J Med Genet 41:387-93. Medline
Dastot-Le Moal et al. 2006. Hum Mutat 28:313-21. Medline
Amiel et al. 2001. Am J Hum Genet 69:1370-77. Medline
 
Myoclonus dystonia

GeneReviews

Resource

159900  SGCE
7q21.3~6% have a detectable deletion20-28% have mutations not detectable by array CGH 
 
 
 
 
 
 
Asmus et al. 2007. Brain 130:2736-45. Medline
Grünewald et al. 2008. Hum Mutat 29:331-32. Medline
 
Nablus mask-like facial

608156  Multiple 8q21.3-q22.1Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
 
 
 
 
Shieh et al. 2006. Am J Med Genet 140:1267-73. Medline
 
Nail-patella (NPS)

161200  LMX1B
9q33.31-5% have a detectable deletion~85% have mutations not detectable by array CGH 
 
 
 
 
Dunston et al. 2004. Genomics 84:565-76. Medline
 
Neonatal severe primary hypoparathyroidism (NSHPT)

Resource

239200  CASR
3q21.1UnknownRecessive condition. Allelic with Familial hypocalciuric hypercalcemia 1 (145980). 
 
 
 
 
Pollak et al. 1994. J Clin Invest 93:1108-12. Medline
Ward et al. 2004. J Clin Endocr Metab 89:3721-30. Medline
 
Nephronophthisis 1

Resource

256100  NPHP1
2q1380% have detectable homozygous deletionsRecessive condition. Allelic with Joubert 4 (609583
Saunier et al. 2000. Am J Hum Genet 66:778-89. Medline
 
Nephropathic cystinosis

GeneReviews

219800  CTNS
17p13.340-46% have detectable homozygous deletionsRecessive condition. ~35% have at least one mutation not not detectable by array CGH 
 
 
 
 
 
 
Bendavid et al. 2004. Hum Genet 115:510-14. Medline
Shotelersuk et al. 1998. Am J Hum Genet 63:1352-62. Medline
 
Neurofibromatosis 1 (NF1)/MR

GeneReviews

162200  NF1
17q11.25-20% have a detectable deletion 
Cnossen et al. 1997. Hum Mutat 9:458-64. Medline
Jenne et al. 2003. Genes Chrom & Cancer 37:111-20. Medline
Upadhyaya et al. 1998. Hum Genet 102:591-97. Medline
 
Neurofibromatosis 2 (NF2)

101000  NF2
22q12.215-21% have a detectable deletion34-66% have mutations not detectable by array CGH 
 
 
 
 
Bruder et al. 2001. Hum Mol Genet 10:271-82. Medline
Zucman-Rossi et al. 1998. Hum Mol Genet 7:2095-101. Medline
Evans et al. 2000. J Med Genet 37:897-904. Medline
 
Neurosensory deafness, autosomal recessive (DFNB1)

GeneReviews

220290  GJB6
13q12.11~0.4% have detectable homozygous deletions; ~7.8% have a single detectable deletionRecessive condition. Deletions of GJB6 can also cause phenotype in conjunction with mutations in GJB2. 
 
 
 
 
del Castillo et al. 2002. N Engl J Med 346:243-49. Medline
 
NFIA haploinsufficiency

600727  NFIA
1p31.3Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
 
 
 
 
Lu et al. 2007. PLoS Genet 3:e80. Medline
 
Noonan 1

GeneReviews

163950  PTPN11
12q24.13Precise detection rate unknownMajority have mutations not detectable by array CGH 
Tartaglia et al. 2001. Nat Genet 29:465-68. Medline
 
Noonan 4

610733  SOS1
2p22.1Precise detection rate unknown9-15% have mutations not detectable by array CGH 
 
 
 
 
Roberts et al. 2007. Nat Genet 39:70-74. Medline
Tartaglia et al. 2007. Nat Genet 39:75-79. Medline
 
Norrie

310600  NDP
Xp11.3~15% have a detectable deletion~85% have mutations not detectable by array CGH 
 
 
 
 
Rodriguez-Revenga et al. 2007. Am J Med Genet 143:916-20. Medline
 
Oculocutaneous albinism 2 (OCA2) *

GeneReviews

203200  OCA2
15q13.1Rare homozygous deletions in most ethnicities; ~99% in Navajo populationRecessive condition. 0-91% have at least one mutation not detectable by array CGH depending on ethnicity 
 
 
 
 
 
 
Stevens et al. 1995. Am J Hum Genet 56:586-91. Medline
Yi et al. 2003. Am J Hum Genet 72:62-72. Medline
Suzuki et al. 2003. J Invest Derm 120:781-3. Medline
Akahoshi et al. 2001. Am J Med Genet 104:299-302. Medline
 
Okihiro

607323  SALL4
20q13.2~6% have a detectable deletion63-90% have mutations not detectable by array CGH 
 
 
 
 
Borozdin et al. 2007. Hum Mutat 28:830. Medline
Borozdin et al. 2004. J Med Genet 41:e113. Medline
Kohlhase et al. 2002. Hum Mol Genet 11:2979-87. Medline
 
Opitz

300000  MID1
Xp22.2~2.1% have a detectable deletion~19% have mutations not detectable by array CGH 
Ferrentino et al. 2007. Hum Mutat 28:206-207. Medline
 
Ornithine transcarbamylase deficiency (OTC)

311250  OTC
Xp11.43-12% have a detectable deletion62-92% have mutations not detectable by array CGH 
 
 
 
 
Genet et al. 2000. J Inheit Metab Dis 23:669-76. Medline
Tuchman et al. 1996. Hum Genet 97:274-6. Medline
 
Oro-facio-digital 1 (OFD1)

311200  OFD1
Xp22.2UnknownMajority have mutations not detectable by array CGH 
 
 
 
 
Thauvin-Robinet et al. 2006. J Med Genet 43:54-61. Medline
Morisawa et al. 2004. Hum Genet 115:97-103. Medline
 
Oto-dental

166750  FGF3
11q13.3Precise detection rate unknownAllelic with Congenital deafness with inner ear agenesis, microtia, & microdontia (610706
 
 
 
 
Gregory-Evans et al. 2007. Hum Mol Genet 16:2482-93. Medline
 
Oto-facio-cervical (OFC)

Resource

166780  EYA1
8q13.3Precise detection rate unknownAllelic with Branchio-Oto-Renal (BOR)/Melnick-Fraser (113650
 
 
 
Rickard et al. 2001. Hum Genet 108:398-403. Medline
 
Pallister-Killian *

Resource

601803  Multiple 12pPrecise detection rate unknownTetrasomy 12p is detectable by SignatureChip® 
Ballif et al. 2006. Am J Med Genet 140:2757-67. Medline
Van den Veyver et al.  1993.  Am J Med Genet 47:1171-74. Medline
Theisen et al. 2009. Am J Med Genet A 149A:914-8. Medline
 
Parietal foramina 1

GeneReviews

168500  MSX2
5q35.2Precise detection rate unknown~18% have mutations not detectable by array CGH. Allelic with Boston-type craniosynostosis (604757
 
 
 
 
Wilkie et al. 2000. Nat Genet 24:387-90. Medline
Mavrogiannis et al. 2006. Eur J Hum Genet 14:151-58. Medline
 
Parkinsonism with dementia * (FISH)

GeneReviews

605543  SNCA
4q22.1Precise detection rate unknownAvailable as FISH test only. Not routinely tested by the SignatureChip® This test is available as a stand-alone FISH test only.
Ikeuchi et al. 2008. Arch Neurol 65:514-19. Medline
Obi et al. 2008. Neurology 70:238-41. Medline
 
Pelizaeus-Merzbacher *

GeneReviews

312080  PLP1
Xq22.260-70% have a detectable duplication~30% have mutations not detectable by array CGH 
Inoue et al. 1999. Ann Neuro 45:624-32. Medline
Woodward et al. 1998. Am J Hum Genet 63:207-17. Medline
 
Peutz-Jeghers (PJS)

GeneReviews

175200  STK11
19p13.32-9% have a detectable deletion87-95% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Le Meur et al. 2004. Eur J Hum Genet 12:415-18. Medline
Aretz et al. 2005. Hum Mutat 26:513-19. Medline
de Leng et al. 2007. Clin Genet 72:568-73. Medline
 
Pitt-Hopkins

610954  TCF4
18q21.1~33% have a detectable deletion~16% have mutations not detectable by array CGH 
 
 
 
 
Zweier et al. 2007. Am J Hum Genet 80:994-1001. Medline
Amiel et al. 2007. Am J Hum Genet 80:988-93. Medline
Brockschmidt et al. 2007. Hum Mol Genet 16:1488-94. Medline
 
Polycystic kidney disease 1 (PKD1)

GeneReviews

601313  PKD1
16p13.3Rare deletions unless associated with contiguous gene deletion syndromeMajority have mutations not detectable by array CGH. Contiguous gene deletion syndrome also involves Tuberous sclerosis 2 (191100). 
Ariyurek et al. 2004. Hum Mutat 23:99-105. Medline
Brook-Carter et al. 1994. Nat Genet 8:328-32. Medline
Torra et al. 1998. Am J Kidney Dis 31:1038-43. Medline
 
Potocki-Lupski/17p11.2 Microduplication *

610883  Multiple 17p11.2~99% have a detectable duplicationCandidate gene RAI1 (607642). 
Potocki et al. 2000. Nat Genet 24:84-87. Medline
Potocki et al. 2007. Am J Hum Genet 80:633-49. Medline
 
Potocki-Shaffer

Resource

601224  EXT2
ALX4
11p11.2~99% have a detectable deletion 
Potocki et al. 1996. Am J Med Genet 62:319-25. Medline
Wakui et al. 2005. Eur J Hum Genet 13:528-40. Medline
 
Prader-Willi (PWS)

GeneReviews

176270  SNRPN
15q11.2~70% have a detectable deletion~30% have either maternal UPD or mutations not detectable by array CGH 
Kuwano et al. 1992. Hum Mol Genet 1:417-25. Medline
Magenis et al. 1990. Am J Med Genet 35:333-49. Medline
 
Prader-Willi-like phenotype

Resource

176270  SIM1
6q16.3Deletions uncommon 
 
 
 
Faivre et al. 2002. J Med Genet 39:594-96. Medline
 
Proteus/Proteus-like

176920  PTEN
10q23.31UnknownAllelic with Bannayan-Riley-Ruvalcaba (153480)/Cowden (158350)/Macrocephaly/autism (605309). 
 
 
 
 
Smith et al. 2002. J Med Genet 39:937-40. Medline
Zhou et al. 2000. Hum Molec Genet 9:765-68. Medline
 
PTEN Hamartoma Tumor syndrome

SignatureChip® Detection Rates for PTEN Hamartoma Tumor Syndrome and Allelic Disorders

PTEN Hamartoma Tumor Syndrome is a syndrome that incorporates several disorders with phenotypic overlap caused by mutations in PTEN, including Bannayan-Riley Ruvalcaba syndrome, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome. While these disorders have specific distinguishing characteristics, they have features in common and recommended management is virtually identical for all.

2-11% of cases of Bannayan-Riley-Ruvalcaba syndrome (BRRS) are caused by deletions of the PTEN gene, the majority of which are detectable by array CGH technology. Approximately 60% have identifiable PTEN point mutations. Subjects with this condition often have autistic features, macrocephaly, hamartomatous intestinal polyps, lipomas and penile freckling.

~1% of Cowden syndrome (CS) are caused by deletions of the PTEN gene, the majority of which are detectable by array CGH technology. Approximately 80% have identifiable PTEN point mutations that are not detectable by array CGH. Subjects with this condition may have cancers of the breast, uterus, thyroid, and urogenital tract as well as macrocephaly, Lhermitte-Duclos disease (macrocephaly, seizures, and mental retardation associated with dysplastic gangliocytoma of the cerebellum), specific skin lesions (e.g., trichelemmomas, lipomas), hamartomatous polyps, fibrocystic breasts, and urogenital system malformations and tumors. Autistic-like tendencies have also been reported in some patients.

No large deletions have been reported in cases of Proteus syndrome or Proteus-like syndrome. However, this disorder has phenotypic overlap with BRRS and CS and is considered part of the PTEN Hamartoma Tumor Syndrome Spectrum. Detection rates for point mutations are not reported consistently, implying a possible second locus for these syndromes. These are disorders of mosaic, progressive overgrowth, including connective tissue nevi, macrocephaly, ovarian and parotid tumors, atypical adipose tissue growth, and vascular malformations.

While Macrocephaly/autism syndrome is not considered part of the PTEN Hamartoma Tumor Syndrome, it is allelic to these tumor syndromes and has the overlapping phenotype of both macrocephaly and autistic-like features. Approximately 4% of patients with a head circumference >2 standard deviations above the mean and autism spectrum disorder have point mutations in PTEN, that are not detectable by array CGH.

Renal cysts and diabetes (RCAD) *

137920  HNF1B
17q1222% have a detectable deletion~45% have mutations not detectable by array CGH 
 
 
 
 
Bellanné-Chantelot et al. 2005. Diabetes 54:3126-32. Medline
 
Retinoblastoma/MR

GeneReviews

180200  RB1
13q14.280% have a detectable deletion3-5% of bilateral and unilateral isolated RB cases have deletions 
Cowell et al. 1989.Opthalmic Paediatr Genet 10:117-27. Medline
Richter et al. 2003. Am J Hum Genet 72:253-69. Medline
 
Rieger 1 (RIEG1)

Resource

180500  PITX2
4q25Unknown~40% have mutations not detectable by array CGH 
 
 
 
Amendt et al. 2000. Cell Mol Life Sci 57:1652-66. Medline
Flomen et al. 1998. Genomics 47:409-13. Medline
Lines et al. 2004. Invest Ophthalmol Vis Sci 45:828-33. Medline
 
Rubinstein-Taybi (RTS)

180849  CREBBP
16p13.311% have a detectable deletion~10% have mutations not detectable by array CGH. Phenotypic overlap with 16p13.3 Microdeletion/Severe Rubenstein-Taybi (610543). 
Petrij et al. 2000. J Med Genet 37:168-76. Medline
Taine et al. 1998. Am J Med Genet 78:267-70. Medline
 
Saethre-Chotzen

GeneReviews

101400  TWIST1
7p21.111-18% have a detectable deletion~25% have mutations not detectable by array CGH 
Cai et al. 2003. Hum Genet 114:68-76. Medline
Chun et al. 2002. Am J Med Genet 110:136-43. Medline
 
Schizencephaly

Resource

269160  EMX2
10q26.11Unknown~10% have mutations not detectable by array CGH 
 
 
 
 
Faiella et al. 1997. Eur J Hum Genet 5:186-90. Medline
Tietjen et al. 2007. Am J Med Genet 143:1313-16. Medline
 
Senior-Loken 6

Resource

610189  CEP290
12q21.32UnknownRecessive condition. ~3% have at least one mutation not detectable by array CGH. Allelic with Joubert 5 (610188)/Leber congenital amaurosis X (611755)/Meckel 4 (611134). 
 
 
 
 
Helou et al. 2007. J Med Genet 44:657-63. Medline
 
Severe myoclonic epilepsy of infancy (SMEI)

607208  SCN1A
2q24.32% have a detectable deletion~33-35% have mutations not detectable by array CGH. Allelic with Generalized epilepsy with febrile seizures plus 2 (604233). 
 
 
 
 
Suls et al. 2006. Hum Mutat 27:914-20. Medline
Nabbout et al. 2003. Neurology 60:1961-67. Medline
 
Sex reversal, autosomal dominant 2 (SRA2)

154230  Multiple 9p24.3Precise detection rate unknownCandidate gene DMRT1 (602424
 
 
 
Huret et al. 1988. J Med Genet 25:741-49. Medline
Bennett et al. 1993 J Med Genet 30:518-20. Medline
Flejter et al. 1998. Am J Hum Genet 63:794–802. Medline
Raymond et al. 1999 Hum Molec Genet 8:989-96. Medline
 
Short stature, pituitary and cerebellar defects, small sella turcica

Resource

262700  LHX4
1q25.2Unknown 
 
 
 
 
Machinis et al. 2001. Am J Hum Genet 69:961-68. Medline
Tajima et al. 2007. Endocr J 54:637-41. Medline
 
Simpson-Golabi-Behmel (SGBS)

GeneReviews

312870  GPC3
Xq26.2Precise detection rate unknown~70% have mutations not detectable by array CGH 
 
 
 
 
 
 
Mariani et al. 2003. J Pediatr Endocrinol Metab 16:225-32. Medline
Hughes-Benzie et al. 1996. Am J Med Genet 66:227-34. Medline
Li et al. 2001. Am J Med Genet 102:161-68. Medline
Veugelers et al. 2000. Hum Mol Genet 9:1321-28. Medline
 
Smith-Lemli-Opitz (SLOS)

270400  DHCR7
11q13.4UnknownRecessive condition. 88-93% have at least one mutation not detectable by array CGH 
 
 
 
 
Witsch-Baumgartner et al. 2000. Am J Hum Genet 66:402-12. Medline
Yu et al. 2000. Hum Mol Genet 9:1385-91. Medline
 
Smith-Magenis (SMS)

GeneReviews

182290  RAI1
17p11.290-99% have a detectable deletionVery few have mutations not detectable by array CGH 
Greenberg et al. 1991. Am J Hum Genet 49:1207-18. Medline
Seranski et al. 1999. Genomics 56:1-11. Medline
Slager et al. 2003. Nature Genet. 33:466-68. Medline
Vlangos et al. 2003. Mol Genet Metab 79:134-41. Medline
 
Sotos

GeneReviews

117550  NSD1
5q35.310-40% have a detectable deletion depending upon ethnicity14-90% have mutations not detectable by array CGH depending upon ethnicity 
Kurotaki et al. 2003. Hum Mutat 22:378-87. Medline
Tatton-Brown et al. 2005. J Med Genet 42:307-13. Medline
Türkmen et al. 2003. Eur J Hum Genet 11:858-65. Medline
Waggoner et al. 2005. Genet Med 7:524-33. Medline
 
Speech & language disorder 1

602081  FOXP2
7q31.1Precise detection rate unknown~2% have mutations not detctable by array CGH 
 
 
 
 
Feuk et al. 2006. Am J Hum Genet 79:965-72. Medline
Lennon et al. 2007. Am J Med Genet A 143:791-98. Medline
MacDermot et al. 2005. Am J Hum Genet 76:1074-80. Medline
 
Split-hand/foot malformation 1 (SHFM1)

Resource

183600  SHFM1
7q21.3Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
 
 
 
Crackower et al. 1996. Hum Mol Genet 5:571-79. Medline
Elliott et al. 2005. Clin Genet 68:408-23. Medline
Scherer et al. 1994. Am J Hum Genet 55:12-20. Medline
Wieland et al. 2004. J Med Genet 41:e54. Medline
 
Split-hand/foot malformation 3 (SHFM3) *

600095  FBXW4
10q24.32Precise detection rate unknownMajority of reported duplications are detectable by array CGH 
 
Elliott et al. 2005. Clin Genet 68:408-23. Medline
de Mollerat et al. 2003. Hum Mol Genet 12:1959-71. Medline
Kano et al. 2005. Hum Genet 118:477-83. Medline
 
Split-hand/foot malformation 4 (SHFM4)

Resource

605289  TP63
3q28Unknown~99% have mutations not detectable by array CGH 
 
 
 
Ianakiev et al. 2000. Am J Hum Genet 67:59-66. Medline
van Bokhoven et al. 2001. Am J Hum Genet 69:481-92. Medline
 
Split-hand/foot malformation 5 (SHFM5)

Resource

606708  DLX1
DLX2
2q31.1Precise detection rate unknown 
 
 
 
Bijlsma et al. 2005. Prenat Diag 25:39-44. Medline
Boles et al. 1995. Am J Med Genet 55:155-60. Medline
Duijf et al. 2003. Hum Mol Genet 12:R51-60. Medline
 
SRY Dosage Abnormalities

SignatureChip® Detection Rates/Fact Sheet for SRY Dosage Abnormalities

The sex determining region (SRY) gene is located on Yp11.31. Dosage abnormalities of SRY (i.e. loss of SRY on the Y chromosome or presence of SRY on other chromosomes) are responsible for disorders of sexual differentiation., such as XX male syndrome and XY gonadal dysgenesis.

XX male syndrome: XX karyotype with male phenotype (external genitalia normal to ambiguous, normal testicles, azoospermia, lacking internal female structures).

80% of XX males have SRY. Typically, XX males with SRY have normal external genitalia and develop gynecomastia around the time of puberty. Presence of SRY on an X chromosome is typically due to interchange between pseudoautosomal regions on the X and Y p-arms.

20% of XX males have no SRY. Typically, XX males with no SRY have some level of genital ambiguity and are more likely to have gynecomastia prior to puberty. The cause of masculinization in these individuals is not well understood. Explanations for some cases may include: low level XX/XY or XX/XXY mosaicism which is known to cause overlapping features, SOX9 duplication on chromosome 17q (one case has been reported; Medline), or autosomal recessive inheritance (one large family has been reported; Medline).

XY females: XY karyotype with female phenotype (range of normal primary and secondary sexual characteristics, defined by individual syndrome).

Loss of SRY on the Y chromosome causes XY gonadal dysgenesis, also called Swyer syndrome, causing failure of pubertal development, lack of external secondary sexual characteristics, and streak gonads internally with an increased risk for gonadoblastoma.  Expressivity in families is variable.

10-15% of females with XY gonadal dysgenesis have a deletion of SRY, while an additional 10-15% have an SRY point mutation.  Females with XY gonadal dysgenesis and no SRY abnormalities may have mutations in other genes, such as deletion of the DMRT1 and/or DMRT2 genes on chromosome 9p which has been rarely reported (Medline), but other etiologies are not well known.

XY females with other phenotypes include Androgen insensitivity syndrome (AIS), caused by mutations in the androgen receptor gene, as well as disorders causing extragonadal defects in addition to the female phenotype, such as Campomelic dysplasia.

Steroid sulfatase deficiency

Resource

308100  STS
Xp22.3180-90% have a detectable deletion10-20% have mutations not detectable by array CGH 
Ballabio et al. 1989. Genomics 4:36-40. Medline
Conary et al. 1987. Biochem Biophys Res Commun 144:1010-17. Medline
Kashork et al. 2002. Prenat Diag 22:1028-32. Medline
Shapiro et al. 1989. Proc Nat Acad Sci USA 86:8477-81. Medline
 
Stickler I

108300  COL2A1
12q13.11Rare deletions 
 
 
 
 
Miyake et al. 2004. J Hum Genet 49:282-84. Medline
Richards et al. 2007. Hum Mutat 28:639. Medline
 
Synpolydactyly/Syndactyly II

Resource

186000  HOXD gene cluster 2q31.1Deletions uncommonMajority have mutations not detectable by array CGH. 
 
Goodman. 2002. Am J Med Genet 112:256-65. Medline
Goodman et al. 2002. Am J Hum Genet 70:547-55. Medline
 
Townes-Brocks 1

107480  SALL1
16q12.1~1% have a detectable deletionMinor phenotypic overlap with 16q11.2-q12.2 Microdeletion 
 
 
 
 
Borozdin et al. 2006. Hum Mutat 27:211-12. Medline
Marlin et al. 1999. Hum Mutat 14:377-86. Medline
Botzenhart et al. 2005. Hum Mutat 26:282. Medline
 
Trichorhinophalangeal 1

Resource

190350  TRPS1
8q23.3<20% have a detectable deletion>80% have mutations not detectable by array CGH 
Ludecke et al. 2001. Am J Hum Genet 68: 81-91. Medline
Momeni et al. 2000. Nat Genet 24:71-74. Medline
 
Tuberous sclerosis 1 (TSC1)

GeneReviews

191100  TSC1
9q34.13Deletions uncommon17-26% have mutations not detectable by array CGH 
 
 
 
 
 
 
Kozlowski et al. 2007. Hum Genet 121:389-400. Medline
Nellist et al. 2005. Genet Test 9:226-30. Medline
Au et al. 2007. Genet Med 9:88-100. Medline
Devlin et al. 2006. Dev Med Child Neurol 48:495-99. Medline
 
Tuberous sclerosis 2 (TSC2)

GeneReviews

191100  TSC2
16p13.310-30% have a detectable deletion~60% have mutations not detectable by array CGH 
Sampson et al. 1997. Am J Hum Genet 61:843-51. Medline
van Bakel et al. 1997. Hum Mol Genet 6:1409-14. Medline
 
Ulnar-mammary

Resource

181450  TBX3
12q24.21Deletions uncommonMajority have mutations not detectable by array CGH 
 
 
 
 
Borozdin et al. 2006. Am J Med Genet 140:1880-86. Medline
Klopocki et al. 2006. Eur J Hum Genet 14:1274-79. Medline
Bamshad et al. 1999. Am J Hum Genet 64:1550-62. Medline
 
Van der Woude

GeneReviews

119300  IRF6
1q32.22-3% have a detectable deletion~43% have mutations not detectable by array CGH 
 
 
 
 
Schutte et al. 1999. Am J Med Genet 84:145-50. Medline
Kondo et al. 2002. Nat Genet 32:285-89. Medline
 
Vascular endothelial growth factor (VEGFA)-related disorders

192240  VEGFA
6p21.1Rare deletions 
 
 
 
 
Izumi et al. 2006. Am J Med Genet 140:398-401. Medline
 
von Hippel-Lindau

GeneReviews

193300  VHL
3p25.3~2.5% have a detectable deletion76-88% have mutations not detectable by array CGH 
 
 
 
 
Huang et al. 2007. Eur J Clin Invest 37:492-500. Medline
Richards et al. 1993. Hum Mol Genet 2:879-82. Medline
 
Waardenburg I

GeneReviews

193500  PAX3
2q36.10.7-1.3% have a detectable deletion80% have mutations not detectable by array CGH 
 
 
 
 
Tassabehji et al. 1995. Hum Mol Genet 4:2131-37. Medline
Milunsky et al. 2007. Genet Test 11:179-182. Medline
 
Waardenburg IIA

Resource

193510  MITF
3p14.1Precise detection rate unknown~22% have mutations not detectable by array CGH 
 
 
 
 
Tassabehji et al. 1995. Hum Mol Genet 4:2131-37. Medline
Schwarzbraun et al. 2007. Am J Med Genet 143:619-24. Medline
 
WAGR

GeneReviews

194072  PAX6
WT1
11p13~66% have a detectable deletion 
Crolla et al. 2002. Am J Hum Genet 71:1138-49. Medline
 
Walker-Warburg, LARGE-related

Resource

236670  LARGE
22q12.3Rare deletionsRecessive condition. 
 
 
 
 
 
 
 
van Reeuwijk et al. 2007. Hum Genet 121:685-90. Medline
Longman et al. 2003. Hum Mol Genet 12:2853-61. Medline
 
Williams-Beuren

GeneReviews

194050  ELN
7q11.23>95% have a detectable deletion 
Lowery et al. 1995. Am J Hum Genet 57:49-53. Medline
Nickerson et al. 1995. Am J Hum Genet 56:1156-61. Medline
 
Wilms Tumor 1

GeneReviews

194070  WT1
11p13Rare deletions unless associated with contiguous gene syndromeMajority have mutations not detectable by array CGH. Contiguous gene deletion syndrome involves WAGR (194072). 
Royer-Pokora et al. 2004. Am J Med Genet 127:249-57. Medline
 
Wolf-Hirschhorn

194190  Multiple 4p16.3>95% have a detectable deletion 
Altherr et al. 1997. Am J Med Genet 71:47-53. Medline
Battaglia et al. 2001. Adv Pediatr 48:75-113. Medline
Van Buggenhout et al. 2004. J Med Genet 41:691-98. Medline
 
X-linked agammaglobulinemia

GeneReviews

300755  BTK
Xq22.1Precise detection rate unknown~93% have mutations not detectable by array CGH 
 
 
 
 
Šedivá et al. 2007. J Clin Immunol 27:640-46. Medline
Conley et al. 1998 Am J Hum Genet 62:1034-43. Medline
Richter et al. 2001. Pediatr Allergy Immunol 12:107-11. Medline
 
X-linked Alport (ATS)

GeneReviews

301050  COL4A5
Xq22.3~5.7% have a detectable deletion 
 
 
 
 
 
 
Jais et al. 2000. J Am Soc Neph 11:649–57. Medline
Antignac et al. 1994. J Clin Invest 93:1195-207. Medline
 
X-linked Alport plus diffuse leiomyomatosis (ATS-DL)

301050  COL4A5
COL4A6
Xq22.3~99% have a detectable deletionDeletions of COL4A5 that also disrupt COL4A6 are responsible for DL phenotype; deletions of COL4A5 that also encompass COL4A6 cause isolated X-linked Alport. 
 
 
 
 
 
 
 
Heidet et al. 1995. Hum Mol Genet 4:99-108. Medline
 
X-linked chronic granulomatous disease

Resource

306400  CYBB
Xp11.4~5% have a detectable deletion~89% have mutations not detectable by array CGH 
 
 
 
 
 
 
 
Rae et al. 1998. Am J Hum Genet 62:1320-31. Medline
 
X-linked heterotaxy

Resource

306955  ZIC3
Xq26.3Deletions uncommon~4% have mutations not detectable by array CGH 
Ferrero et al. 1997. Am J Hum Genet 61:395-401. Medline
Ware et al. 2004. Am J Hum Genet 74:93-105. Medline
 
X-linked hydrocephalus and nephrogenic diabetes insipidus

  L1CAM
AVPR2
Xq28Precise detection rate unknownContiguous gene deletion causing X-linked hydrocephalus (307000) and nephrogenic diabetes insipidus (304800
 
 
 
 
 
 
Tegay et al. 2007. Am J Med Genet 143:594-98. Medline
Knops et al. 2008. Am J Med Genet 146:1853-58. Medline
 
X-linked idiopathic short stature (ISSX)

GeneReviews

300582  SHOX
Xpter-Xp22.3 & Ypter-Yp11.322-14% have a detectable deletion0.4-12% have mutations not detectable by array CGH. Allelic with Langer mesomelic dysplasia (249700)/Leri-Weill dyschondrosteosis (127300). 
Huber et al. 2006. J Med Genet 43:735-39. Medline
Schneider et al. 2005. Am J Hum Genet 77:89-96. Medline
Rappold et al. 2002. J Clin Endocr Metab 87:1402-406. Medline
 
X-linked infantile spasms, ARX-related

Resource

308350  ARX
Xp21.3Unknown~80% have mutations not detectable by array CGH. Allelic with X-linked mental retardation 54 (300419)/X-linked lissencephaly with ambiguous genitalia (300215). 
 
 
 
 
Strømme et al. 2002. Nat Genet 30:441-45. Medline
 
X-linked infantile spasms, CDKL5-related

300672  CDKL5
Xp22.13Deletions uncommon5-7% have mutations not detectable by array CGH 
 
 
 
 
Van Esch et al. 2007. Am J Med Genet 143:364-69. Medline
Scala et al. 2005. J Med Genet 42:103-107. Medline
Archer et al. 2006. J Med Genet 43:729-34. Medline
 
X-linked juvenile retinoschisis

312700  RS1
Xp22.13Rare deletions~91% have mutations not detectable by array CGH 
 
 
 
 
den Dunnen et al. 1998. Hum Mol Genet 7:1185-92. Medline
Huopaniemi et al. 2000. Hum Mutat 16:307-14. Medline
 
X-linked lissencephaly

Resource

300067  DCX
Xq22.3Unknown20-38% have mutations not detectable by array CGH 
 
 
 
Dobyns et al. 1996. Neurology 47:331-39. Medline
Pilz et al. 1998. Hum Mol Genet 7:2029-37. Medline
 
X-linked lissencephaly with ambiguous genitalia

Resource

300215  ARX
Xp21.3Unknown~87.5% have mutations not detectable by array CGH. Allelic with X-linked mental retardation 54 (300419)/X-linked infantile spasms, ARX-related (308350). 
 
 
 
 
Kato et al. 2004. Hum Mutat 23:147-59. Medline
 
X-linked lymphoproliferative (XLP)

GeneReviews

308240  SH2D1A
Xq254-9% have a detectable deletion16-89% have mutations not detectable by array CGH depending on features 
 
 
 
 
Sumegi et al. 2000. Blood 96:3118-25. Medline
Arico et al. 2001. Blood 97:1131-33. Medline
 
X-linked mental retardation 21

Resource

300143  IL1RAPL1
Xp21.3Precise detection rate unknownMajority of reported deletions are detectable by array CGH 
Zhang et al. 2004. Hum Mutat 24:273. Medline
Jin et al. 2000. Eur J Hum Genet 8:87-97. Medline
 
X-linked mental retardation 30

Resource

300558  PAK3
Xq22.3UnknownRare mutations not detectable by array CGH 
 
 
 
Allen et al. 1998. Nat Genet 20:25-30. Medline
Rifé et al. 2000. Am J Med Genet 94:389-91. Medline
 
X-linked mental retardation 54

Resource

300419  ARX
Xp21.3Unknown~2% have mutations not detectable by array CGH. Allelic with X-linked infantile spasms, ARX-related (308350)/X-linked lissencephaly with ambiguous genitalia (300215). 
 
 
 
 
Bienvenu et al. 2002. Hum Mol Genet 11:981-91. Medline
 
X-linked mental retardation with isolated growth hormone deficiency *

Resource

300123  SOX3
Xq27.1Precise detection rate unknownMany reported deletions and duplications are detectable by array CGH 
 
 
 
Laumonnier et al. 2002. Am J Hum Genet 71:1450-55. Medline
Raynaud et al. 1998. Am J Med Genet 76:255-61. Medline
Woods et al. 2005. Am J Hum Genet 76:833-49. Medline
 
X-linked mental retardation with microcephaly & disproportionate pontine and cerebellar hypoplasia

300172  CASK
Xp11.4~4% have a detectable deletion~4% have mutations not detectable by array CGH 
 
 
 
 
Froyen et al. 2007. Hum Mutat 28:1034-42. Medline
Hayashi et al. 2008. Am J Med Genet A. 146:2145-51. Medline
Najm et al. 2008. Nat Genet - Epub ahead of print. Medline
 
XX male

278850  SRY
Yp11.3120% have absent SRY 
 
 
 
 
McElreavey & Cortes 2001. Semin Reprod Med 19:133-39. Medline
Müller et al. 1987. Development 101 Suppl:51-58. Medline
 
XY gonadal dysgenesis

400044  SRY
Yp11.31Large deletions uncommon20-30% have small deletions or mutations not detectable by array CGH 
 
 
 
 
Scherer et al. 1998. Cytogenet Cell Genet 80:188-92. Medline
McElreavey et al. 1992. Proc Natl Acad Sci USA 89:11016-20. Medline
 
XY sex-reversal, +/- adrenal failure

GeneReviews

184757  NR5A1
9q33.3Precise detection rate unknown~13% have mutations not detectable by array CGH 
 
 
 
 
Schlaubitz et al. 2007. Am J Med Genet 143:1071-81. Medline
Lin et al. 2007. J Clin Endocrinol Metab 92:991-99. Medline
 
All 41 unique subtelomeric regions

  Multiple 41 sites0.5-7% have a detectable deletion 
Knight et al. 2000. Am J Hum Genet. 67:320-32. Medline
Ravnan et al. 2005. J Med Genet. 43:478-89. Medline
Veltman et al. 2002. Am J Hum Genet 5:1269-76. Medline
Wong et al. 2005. Genet Med 7:264-71. Medline
 
All 43 unique pericentromeric regions

  Multiple 43 sitesDetection rate variable depending upon the marker chromosome 
 
Aneuploidy

  Multiple 24 chromosomes>99% detectable by microarray 
Ballif et al. 2006. Prenat Diagn 26:333-39. Medline
Schaeffer et al. 2004. Am J Hum Genet 74:1168-74. Medline
 

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