A novel GJA8 mutation causing a recessive triangular cataract

PURPOSE: The aim of the study was to characterize the underlying mutation in a consanguineous family having cataracts. METHODS: Family D having congenital cataracts was treated at the University Eye Clinics at Giessen (Germany). Lens material from surgeries was collected, immediately frozen at –80 °C, and used for cDNA production. Blood was taken from the proband and available family members. Polymerase chain reaction (PCR)-amplified DNA fragments were characterized by sequencing and restriction digestion. RESULTS: The proband, AD, has a dense, triangular nuclear cataract. The parents are consanguineous, and the mother and grandmother suffer from a discrete, symmetric opacity of the fetal lens nucleus. The proband’s lens cDNA showed a homozygous insertion of one G after position 776 of the GJA8 gene, leading to a frame shift and 123 novel amino acids. The homozygous mutation was confirmed in the genomic DNA and is also present in the cataract-operated brother of the proband; all other family members investigated were heterozygous. The mutation could not be detected in 96 healthy controls from Germany. CONCLUSIONS: The ins776G mutation most likely causes a recessive triangular cataract with variable expressivity of a weak phenotype in heterozygotes.