Identification of novel mutations causing pediatric cataract in Bhutan, Cambodia, and Sri Lanka

• Published in: Molecular genetics & genomic medicine Vol. 6; no. 4; pp. 555 - 564
• Main Authors: Javadiyan, Shari, Lucas, Sionne E. M., Wangmo, Dechen, Ngy, Meng, Edussuriya, Kapila, Craig, Jamie E., Rudkin, Adam, Casson, Robert, Selva, Dinesh, Sharma, Shiwani, Lower, Karen M., Meucke, James, Burdon, Kathryn P.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2018; John Wiley and Sons Inc
• Subjects: Blindness; Cataracts; Children; congenital cataract; Gene sequencing; Genes; Identification methods; inherited eye disease; Mutation; mutation screening; next‐generation sequencing; Original; Patients; Pediatrics; People with disabilities; Proteins; Schools; Cambodia; Sri Lanka; Bhutan; mutation screening; congenital cataract; inherited eye disease; next-generation sequencing
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.406

Background Pediatric cataract is an important cause of blindness and visual impairment in children. A large proportion of pediatric cataracts are inherited, and many genes have been described for this heterogeneous Mendelian disease. Surveys of schools for the blind in Bhutan, Cambodia, and Sri Lanka have identified many children with this condition and we aimed to identify the genetic causes of inherited cataract in these populations. Methods We screened, in parallel, 51 causative genes for inherited cataracts in 33 probands by Ampliseq enrichment and sequencing on an Ion Torrent PGM. Rare novel protein coding variants were assessed for segregation in family members, where possible, by Sanger sequencing. Results We identified 24 rare (frequency <1% in public databases) or novel protein coding variants in 12 probands and confirmed segregation of variants with disease in the extended family where possible. Of these, six are predicted to be the cause of disease in the patient, with four other variants also highly likely to be pathogenic. Conclusion This study found that 20%–30% of patients in these countries have a mutation in a known cataract causing gene, which is considerably lower than the 60%–70% reported in Caucasian cohorts. This suggests that additional cataract genes remain to be discovered in this cohort of Asian pediatric cataract patients. We screened 51 known congenital or pediatric cataract genes in 33 probands from Bhutan, Cambodia, and Sri Lanka. We identified likely causative mutations in six individuals. This much lower rate than that observed in European patients indicates there are additional genetic causes of cataract in these countries yet to be identified.