Application of WES Towards Molecular Investigation of Congenital Cataracts: Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India

• Published in: International journal of molecular sciences Vol. 21; no. 24; p. 9569
• Main Authors: Kandaswamy, Dinesh Kumar, Prakash, Makarla Venkata Sathya, Graw, Jochen, Koller, Samuel, Magyar, István, Tiwari, Amit, Berger, Wolfgang, Santhiya, Sathiyaveedu Thyagarajan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.12.2020; MDPI
• Subjects: Alleles; Blindness; Cataract - genetics; Cataract - pathology; Cataracts; congenital cataract; Congenital diseases; Disease; Documentation; EPHA2; EphA2 protein; Ephrin-A2 - genetics; Families & family life; Family medical history; Female; FYCO1; Genes; Genetic Testing; Heredity; Heterogeneity; Humans; Identification; Male; Microtubule-Associated Proteins - genetics; Mutation; Nuclear Receptor Coactivators - genetics; Nuclear receptors; P3H2; PAX6; Pax6 protein; PAX6 Transcription Factor - genetics; Pedigree; Procollagen-Proline Dioxygenase - genetics; Receptor mechanisms; Ribonucleoproteins - genetics; Transcription; WES; Whole Genome Sequencing; India; FYCO1; WES; NCOA6; hearing and speech impairment; P3H2; PAX6; TDRD7; clinical heterogeneity; congenital cataract; EPHA2; genetic heterogeneity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21249569

Congenital cataracts are the prime cause for irreversible blindness in children. The global incidence of congenital cataract is 2.2-13.6 per 10,000 births, with the highest prevalence in Asia. Nearly half of the congenital cataracts are of familial nature, with a predominant autosomal dominant pattern of inheritance. Over 38 of the 45 mapped loci for isolated congenital or infantile cataracts have been associated with a mutation in a specific gene. The clinical and genetic heterogeneity of congenital cataracts makes the molecular diagnosis a bit of a complicated task. Hence, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 11 pedigrees affected with familial congenital cataracts. Analysis of the WES data for known cataract genes identified causative mutations in six pedigrees (55%) in (two variants) , and an additional likely causative mutation in a novel gene , which represents the first dominant mutation in this gene. This study identifies a novel cataract gene not yet linked to human disease. NCOA6 is a transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator function.