Familial Recurrence of SOX2 Anophthalmia Syndrome: Phenotypically Normal Mother With Two Affected Daughters

The SOX2 anophthalmia syndrome is emergin as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia/microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband. (c) 2008 Wiley-Liss, Inc.