Mutations in crystallin genes result in congenital cataract associated with other ocular abnormalities

Purpose This study aims to describe the phenotypes and identify pathogenic mutations in Chinese patients who have congenital cataracts associated with other ocular abnormalities. Methods Eleven patients from four unrelated Chinese families plus two simplex cases were enrolled in this study. Detailed ophthalmic examinations were performed. DNA samples were isolated from peripheral blood collected from the patients. Next-generation sequencing of known ocular genes was applied to the proband of each family and two simplex cases to find pathogenic variances. PCR and Sanger sequencing were conducted for validation and segregation tests. Results All 13 patients had congenital cataracts, and other ocular abnormalities were found in some cases. Microcornea was found in 12 subjects, and ocular coloboma was observed in five. Various types of coloboma, including iris, choroid, macular, and optic disc, were described. Five mutations in crystallin genes were identified. Four of the mutations are novel: CRYBB1: p.(Arg230Cys), CRYBB2: p.(Gly149Val), CRYGC: p.(Met44CysfsTer59), and CRYGC: p.(Tyr144Ter). One mutation was reported previously: CRYAA: p.(Arg21Trp). Conclusions We examined a cohort of Chinese patients with congenital cataracts and studied the phenotypes and genotypes. Extralenticular abnormalities, such as microcornea and ocular coloboma, can also be found in patients with congenital cataracts. The phenotype of congenital cataracts associated with macular and optic disc coloboma was reported for the first time in this study. Four novel mutations and one previously reported mutation were identified. These data expand the mutation spectrum in crystallin genes and enhance our understanding of the phenotypes of congenital cataracts.