Objective: To identify the gene mutation in a four-generation Chinese family with autosomal dominant congenital cataract associated with microcornea.
Methods: Experimental research. Twelve members in this family (including six affected and six unaffected individuals) were enrolled into this study. They underwent full ophthalmological and clinical examinations to rule out any concomitant disorders. Blood samples were collected and genomic DNA was extracted. Microsatellite markers near the reported loci, which are associated with congenital cataract and microcornea were selected and amplified from DNA samples using polymerase chain reaction. Linkage analysis was performed. The exons and exon/intron junction of candidate gene in the related chromosome were sequenced. The product of the first exon was digested by ApaL I restriction enzyme to certify the mutation.
Results: The phenotype studied in this family was nuclear cataract accompanied with microcornea. At markers D21S1885 and D21S1890 near the locus 21q22.3, the affected members had the same allele, but the unaffected did not. The Lod scores were 2.11 in both markers, indicating that this locus were linked to the congenital cataract in this family. DNA sequencing of candidate gene CRYAA showed a heterozygous mutation c.34C > T in exon 1, which led to condon 12 in peptide chain encoding arginine substituted by cysteine. ApaL I enzyme digestion certified that all of the affected members had the same mutation c.34C > T, but the unaffected and normal individuals did not.
Conclusion: Mutation (p.R12C) of CRYAA is the genetic change that causes the occurrence of congenital cataract with microcornea in this family.