SignatureChip® Detection Rates for Holoprosencephaly

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

Condition OMIM# Gene/ Locus Location Detection rate for deletion/duplication by microarray Comments References

*  Duplication of this region is 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.

Information based on UCSC Genome Browser, March 2006 Assembly

Holoprosencephaly 1

GeneReviews
236100 TMEM1 21q22.3 Unknown   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

GeneReviews
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

GeneReviews
142945 SHH 7q36.3 1-2% have a detectable deletion 6-8% 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

GeneReviews
142946 TGIF 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

Gripp et al. 2000. Nat Genet 25:205-208. Medline

Ming et al. 2002. Am J Hum Genet 71:1017-32. Medline
Holoprosencephaly 5

GeneReviews
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

Brown et al. 2001. Hum Molec Genet 10:791-96. Medline

Dubourg et al. 2004. Hum Mutat 24:43-51. Medline
Holoprosencephaly 6

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

GeneReviews
601309 PTCH1 9q22.32 Unknown Allelic with Basal cell nevus/Gorlin-Goltz (109400) Ming et al. 2002. Hum Genet 110:297-301. Medline
Holoprosencephaly 8

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

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

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