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A. S. Schneider, T. M. Bardakjian, L. M. Reis, R. C. Tyler, E. V. Semina; Screening of SOX2 in Patients With Anophthalmia/Microphthalmia: Identification of New Mutations. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1305. doi: https://doi.org/.
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SOX2 anophthalmia syndrome is a relatively well-described syndrome characterized by bilateral anophthalmia/microphthalmia, learning disabilities, motor delay, brain malformations and micropenis or genital anomalies in males. SOX2 anophthalmia syndrome is considered to be an autosomal dominant condition with most cases resulting from a de novo mutation. Previous studies have reported that using sequence analysis alone 10-15% of individuals with bilateral severe eye malformations and fewer than 3% of individuals with unilateral eye involvement are found to have a heterozygous loss-of-function mutation in the coding region of SOX2 [Fantes et al 2003 ; Ragge et al 2005 ; FitzPatrick, personal observation]. One previous report identified an unaffected mother with mosaicisim for the SOX2 mutation seen in her child.
Sequencing of the SOX2 gene in a cohort of 43 affected individuals was performed.
Sequencing revealed 7 with SOX2 mutations (16%). Five of these individuals had bilateral A/M and two had unilateral A/M. Of the 43 cases screened, 29 had bilateral A/M, 12 had unilateral A/M. There were 2 cases without A/M; one had bilateral aniridia and the other had left anterior segment dysgenesis. Both of those cases were negative for a SOX2 mutation.
The two cases of unilateral A/M both had missense mutations whereas the remainder of mutations caused frameshift and led to premature stop codons, suggesting a potential genotype/phenotype correlation. In addition, 2 of the cases with bilateral A/M identified to have a SOX2 mutation have a sibling with clinically confirmed A/M. Further molecular studies on these families are pending.Detailed clinical phenotypes and corresponding heterozygous mutations will be presented to support our recommendation that all individuals with anophthalmia/microphthalmia with bilateral or unilateral involvement be screened for mutations in SOX2. In addition family studies will be carried out to investigate the possibility of inherited SOX2 mutations in the 2 cases with a significant family history.
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