Mutational spectrum in a Chinese cohort with congenital cataracts

AbstractBackgroundTo identify the mutational spectrum in a Chinese cohort with congenital cataracts.MethodsProbands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel‐based next‐generation sequencing, then classified into a cohort for further mutational analysis.ResultsAfter recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty‐four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified.ConclusionThis study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts.