The mutation spectrum in familial versus sporadic congenital cataract based on next-generation sequencing

Abstract

Abstract Background Congenital cataract (CC) is a significant cause of lifelong visual loss, and its genetic diagnosis is challenging due to marked genetic heterogeneity. The purpose of this article is to report the genetic findings in sporadic and familial CC patients. Methods Patients (n = 53) who were clinically diagnosed with CC and their parents were recruited. Blood samples were collected in our hospital. Mutations were detected by panel-based next-generation DNA sequencing (NGS) targeting 792 genes frequently involved in common inherited eye diseases. Results We identified variants in 10/37 cases (27.02%) of sporadic CC and 14/16 cases (87.5%) of familial CC, which indicated a significant difference (P = 0.000). Of the 13 variants identified in sporadic cases, nine were previously reported mutations, and three were novel mutations, including one de novo mutation (CRYBB2 c.487C > T). The most frequent variants in our cohort were in crystallins and cytoskeletal genes (5/27, 18.52%), followed by proteins associated with X-linked syndromic conditions (14.81%) and transcriptional factors (11.11%). Additional information on the possibility of complications with inherited ocular or systemic diseases other than CC was provided in 17/27 (62.96%) variants. Conclusions These results contribute to expanding the mutation spectrum and frequency of genes responsible for CC. Targeted NGS in CC provided significant diagnostic information and enabled more accurate genetic counselling. This study reports the different distributions of mutation genes in familial and sporadic CC cases.