Faculty Collaboration Database

Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. Am J Med Genet A 2009 Dec;149A(12):2706-15

Date

11/19/2009

Pubmed ID

19921648

Pubmed Central ID

PMC2787970

DOI

10.1002/ajmg.a.33098

Scopus ID

2-s2.0-71949107898 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

SOX2 represents a High Mobility Group domain containing transcription factor that is essential for normal development in vertebrates. Mutations in SOX2 are known to result in a spectrum of severe ocular phenotypes in humans, also typically associated with other systemic defects. Ocular phenotypes include anophthalmia/microphthalmia (A/M), optic nerve hypoplasia, ocular coloboma and other eye anomalies. We screened 51 unrelated individuals with A/M and identified SOX2 mutations in the coding region of the gene in 10 individuals. Seven of the identified mutations are novel alterations, while the remaining three individuals carry the previously reported recurrent 20-nucleotide deletion in SOX2, c.70del20. Among the SOX2-positive cases, seven patients had bilateral A/M and mutations resulting in premature termination of the normal protein sequence (7/38; 18% of all bilateral cases), one patient had bilateral A/M associated with a single amino acid insertion (1/38; 3% of bilateral cases), and the final two patients demonstrated unilateral A/M associated with missense mutations (2/13; 15% of all unilateral cases). These findings and review of previously reported cases suggest a potential genotype/phenotype correlation for SOX2 mutations with missense changes generally leading to less severe ocular defects. In addition, we report a new familial case of affected siblings with maternal mosaicism for the identified SOX2 mutation, which further underscores the importance of parental testing to provide accurate genetic counseling to families.

Author List

Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anophthalmos
Base Sequence
Child
Child, Preschool
DNA Mutational Analysis
Female
Genotype
Humans
Male
Microphthalmos
Molecular Sequence Data
Mutation
Phenotype
SOXB1 Transcription Factors