Novel mutations in CRYGD are associated with congenital cataracts in Chinese families.

Congenital cataract disease is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the genetic defects and to investigate the relationships between disease-causing genes and lens morphology in congenital cataracts. Patients were given a physical examination, and their blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the following candidate genes: CRYGC, CRYGD, CRYGS, GJA8, GJA3 and CRYAA. Mutational analysis of CRYGD identified a recurrent (p.P24T) mutation in two unrelated families with congenital coralliform cataracts and three novel (p.Q101X, p.E104fsX4 and p.E135X) mutations in three families with congenital nuclear cataracts. The p.E135X mutation is a de novo mutation. Haplotype analysis showed patients inherited the same CRYGD allele originated from father. The p.E135X mutation seen in two siblings suggests a mechanism of gonadal mosaicism in the father.