Novel mutations in CRYGC are associated with congenital cataracts in Chinese families

Congenital cataract (CC), responsible for about one-third of blindness in infants, is a major cause of vision loss in children worldwide. 10-25% of CC cases are attributed to genetic causes and CC is a clinically and genetically highly heterogeneous lens disorder in children. Autosomal dominant (AD) inheritance is the most commonly pattern. 195 unrelated non-syndromic ADCC families in this study are recruited from 15 provinces of China. Sanger sequencing approach followed by intra-familial cosegregation, in Silico analyses and interpretation of the variations according to the published guidelines of American College of Medical Genetics (ACMG), were employed to determine the genetic defects. Two mutations (p. Tyr139X and p. Ser166Phe) identified in two unrelated families were associated with their congenital nuclear cataracts and microcornea respectively, which are also reported previously. Six novel CRYGC mutations (p. Asp65ThrfsX38, p. Arg142GlyfsX5, p. Arg142AlafsX22, p. Tyr144X, p. Arg169X, and p. Tyr46Asp) were identified in other six families with congenital nuclear cataracts, respectively. Mutations in the CRYGC were responsible for 4.1% Chinese ADCC families in our cohort. Our results expand the spectrum of CRYGC mutations as well as their associated phenotypes.