Objectives: To report a novel SOX2 (OMIM 184429) mutation in a Chinese family and to describe its ocular and extraocular clinical features. Methods: Ocular and systemic examinations were performed, and genomic DNA was prepared from peripheral leukocytes. The coding exons and the adjacent intronic sequence of SOX2 were analyzed by cycle sequencing. Results: A novel heterozygous c.695CϾA (p.Thr232Asn) mutation in SOX2 was identified in a Chinese family in which both the father and the son had iris and chorioretinal uveal colobomas. In addition, cataracts were noted in the father but not in the son. Other anomalies were not found in the father but were present in the son, including brain arachnoid cyst, microcornea, retrobulbar colobomatous orbital cyst, and penoscrotal hypospadias. This mutation was not detected in the unaffected mother and 103 unaffected control individuals. Conclusions: Mutation in SOX2 is associated with typical ocular coloboma and probably other anomalies in this Chinese family. Arachnoid cyst has not been reported in individuals with the SOX2 mutation. Clinical Relevance: The results remind us that ocular coloboma may be accompanied by arachnoid cyst and may be associated with SOX2 mutation, which will be helpful for improving diagnosis and patient care.

A novel missense mutation, c.428G>A (p.G143E), in the GJA3 gene, localized to the cytoplasmic loop, was suggested to be the genetic cause of congenital nuclear cataract, which further expands the gene mutation spectrum. Our findings suggest that exome sequencing is a powerful and cost-effective tool to discover mutation(s) in disorders with high genetic and clinical heterogeneity. Further functional studies in the GJA3 gene mutations may help uncover pathogenic mechanisms of congenital cataract and therefore provide a possible genetic therapy for this disorder.

Mutations in the ATP-binding cassette, subfamily A, member 4 (ABCA4), elongation of very long chain fatty acids 4 (ELOVL4) and peripherin-2 (PRPH2) genes have been identified in patients with Stargardt macular degeneration (STGD). The aim of this study was to investigate which of these genes is responsible for susceptibility in Chinese patients. A total of 41 probands with STGD or suspected STGD were enrolled in the study. The coding regions and adjacent intronic sequences of the ELOVL4 and PRPH2 genes and 3 coding exons of the ABCA4 gene were amplified by polymerase chain reaction (PCR). The nucleotide sequences of the amplicons were determined by Sanger sequencing. Three novel heterozygous missense mutations in the ABCA4 gene were identified: c:2633C>A (p:Ser878X), c:5646G>A (p:Met1882Ile) and c:6389T>A (p:Met2130Lys). These mutations were not present in 176 normal individuals and were predicted to be pathogenic. Two benign variations were found: a reported variation, c:5682G>C in ABCA4 and a novel variation, c:699G>A in ELOVL4. In addition, 5 single nucleotide polymorphisms (SNPs: rs3812153, rs7764439, rs390659, rs434102 and c:929G>A) were detected in ELOVL4 and PRPH2. The c:929G>A variation has not been previously reported. We conclude that no pathogenic variations in ELOVL4 and PRPH2 were detected in the Chinese STGD patients. Our results imply that ABCA4 is more likely to be significant in Chinese STGD patients.

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal or total blindness. Here, we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4 gene (ABCA4) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype–phenotype relationship. The present study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling.