Abstract
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 PAX6, FYCO1 (two variants), EPHA2, P3H2, TDRD7 and an additional likely causative mutation in a novel gene NCOA6, 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.
Highlights
Congenital cataracts (CC) are the leading cause of significant vision loss, accounting for one-third of childhood blindness globally
It is well known that the best outcome is documented on congenital cataract surgery and optical corrections done before 6-8 weeks of age, emphasizing good ophthalmic examination combined with multi-disciplinary team work to achieve the best possible visual outcomes [4,5]
The present study demonstrated the efficacy of next-generation sequencing (NGS) methods in the genetic diagnosis of inherited congenital cataracts
Summary
Congenital cataracts (CC) are the leading cause of significant vision loss, accounting for one-third of childhood blindness globally. In a recent review on guide to suspect the genetic basis of cataractogenesis, the authors have categorized the genes based on the phenotypes reported in the literature as syndromic cataract (104 genes), genes implicated in syndromes but with reports of only congenital cataracts (8 genes), only cataract causing genes (non-syndromic) (34 genes) and genes that are known to cause cataract along with other eye anomalies (11 genes) [3]. Prompt diagnosis of congenital cataract and knowing its molecular basis enables to achieve optimum visual outcome but aids in further management of the secondary disorders caused during the treatment for the primary disease [4]. Unresolved cases might be instrumental towards the identification of novel disease-associated genes
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