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 | ||||||||||||||||
Information based on UCSC Genome Browser, March 2006 Assembly. |
|||||||||||||||||||||||
 | Holoprosencephaly 1
| 236100 |
TRAPPC10 | 21q22.3 | Unknown | • | • | • | • | • | • | • | • | ||||||||||
 | Holoprosencephaly 2
| 157170 |
SIX3 | 2p21 | ~1% have a detectable deletion | ~4% have mutations not detectable by array CGH | • | • | • | • | • | • | • | • | |||||||||
| Holoprosencephaly 3
| 142945 |
SHH | 7q36.3 | 1-2% have a detectable deletion | 6-8% have mutations not detectable by array CGH | • | • | • | • | • | • | • | • | |||||||||
| Holoprosencephaly 4
| 142946 |
TGIF1 | 18p11.31 | <1% have a detectable deletion | ~1% have mutations not detectable by array CGH | • | • | • | • | • | • | • | • | |||||||||
| Holoprosencephaly 5
| 609637 |
ZIC2 | 13q32.3 | <1% have a detectable deletion | ~3% have mutations not detectable by array CGH | • | • | • | • | • | • | • | • | |||||||||
| Holoprosencephaly 6
| 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
| 610828 |
PTCH1 | 9q22.32 | Unknown | Allelic with Basal cell nevus/Gorlin-Goltz (109400) | • | • | • | • | • | • | • | • |
Ming et al. 2002. Hum Genet 110:297-301. Medline
| ||||||||
| Holoprosencephaly 8
| 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 *
Signature Summary on Holoprosencephaly 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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