Aniridia
Anophthalmia
Microphthalmia
Developmental Eye Disease
- PAX6 (paired box gene 6)
- SOX2 (SRY (sex determining region Y)-box 2)
- SIX6 (sine oculis-related homeobox 6 homolog)
- OTX2 (orthodenticle homolog 2)
- VSX2 (visual system homeobox 2)
- RAX (retina and anterior neural fold homeobox)
- STRA6 (stimulated by retinoic acid gene 6 homolog)
Mutation analysis for five genes involved in development eye disease is offered.
PAX6
It has been estimated that over 80% of patients with aniridia without deletion of the PAX6 gene have a heterozygous mutation identifiable by DNA sequencing as performed by GeneDx. Most of the identified mutations are loss-of-function mutations, including nonsense and frame-shift mutations. Individuals with other developmental eye abnormalities may also have mutation in the PAX6 gene and homozygous PAX6 mutation has been associated with anophthalmia.
SIX6 and SOX2
The etiology of anophthalmia and microphthalmia is heterogeneous and includes chromosomal abnormalities, prenatal exposures, and single gene disorders. Syndromic anophthalmia is associated with mutation in the SOX2 gene. In one study, eleven percent of individuals with sporadic bilateral anophthalmia were found to have a truncating mutation in the SOX2 gene. Whole gene deletions have also been observed in SOX2. Other associated findings were male genitourinary abnormalities, myopathy, and spastic diplegia. Heterozygous deletion of SIX6 has been seen in some cases of bilateral anophthalmia.
OTX2
Haploinsufficiency of OTX2 may be associated with anophthalmia and microphthalmia. OTX2 mutations have also been reported in association with brain malformations and pituitary insufficiency.
VSX2
VSX2 mutations are associated with isolated ocular finding without other systemic malformations.
RAX
Compound heterozygous mutations in the RAX gene have been observed in individuals with anophthalmia with or without scleocornea.
STRA6
Homozygous and compound heterozygous mutations in the STRA6 gene have been observed in individuals with syndromic anophthalmia/microphthalmia. The clinical presentation of individuals with STRA6 mutations is variable with individuals displaying additional features such as: congenital heart defects, cognitive impairment, renal and lung malformations, and dysmorphic facial features among others.
GeneDx offers mutation analysis of the PAX6, SIX6, OTX2, VSX2, SOX2, RAX and STRA6 genes as separate tests. Using genomic DNA obtained from buccal (cheek) swabs or blood (1-5 ml in EDTA), bi-directional sequence analysis of the coding region is offered for PAX6, SOX2, OTX2, VSX2, RAX and STRA6 genes. This analysis is expected to identify most types of mutations with exception of gross deletions. When indicated, targeted array CGH analysis with exon-level resolution (ExonArrayDx) is available to evaluate for a deletion/duplication involving PAX6, SOX2, SIX6, OTX2, or RAX. As VSX2 and STRA6-related anophthalmia is inherited in an autosomal recessive fashion, if sequencing identifies a mutation on a single allele, targeted array CGH analysis will be performed at no additional cost to identify a possible second mutation. Mutation-specific testing and prenatal diagnosis is available once the mutation in a family has been defined.
Aniridia, Iris, Eye, Wilms, WAGR, PAX, SOX, SIX, Anophthalmia, Anopthalmia, Microphthalmia, Micropthalmia, Coloboma, Cataract, Optic nerve
 |
|
© 2000 - 2012 GeneDx. All rights reserved.
|
|
|
