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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®.

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 OS v3
 * Duplication of these regions are associated with a syndrome/clinical phenotype.
(FISH) Available only through SignatureFISH™ testing.

Information based on UCSC Genome Browser, March 2006 Assembly.
Holoprosencephaly 1

236100  Multiple TRAPPC10 candidate
PWP2 candidate 		21q22.3~99% have a detectable deletion 
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Muenke et al. 1995. Am J Hum Genet 57:1074-9. Medline
Nagamine et al. 1997. Biochem Biophys Res Commun 235:185-90. Medline
 
Yamakawa et al. 1995. Hum Mol Genet. 4:709-16. Medline
 
Yamakawa et al. 1996. Cytogenet Cell Genet. 74:140-5. Medline
 
Holoprosencephaly 2

157170  SIX3
2p21~1% have a detectable deletion~4% have mutations not detectable by array CGH 
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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 
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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 
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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 
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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 8

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

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