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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