Open AccessIdentification of novel mutations causing pediatric cataract in Bhutan, Cambodia, and Sri Lanka
Author(s) -
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.
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.406
Subject(s) - cataracts , proband , sanger sequencing , medicine , disease , genetics , blindness , cohort , gene , biology , mutation , optometry , pathology
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.