A recurrent mutation in CRYGD is associated with autosomal dominant congenital coralliform cataract in two unrelated Chinese families

Abstract

Purpose: Congenital cataract is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the mutation responsible for autosomal dominant congenital coralliform cataracts in two Chinese families and to investigate the relationship between virulence genes and lens morphology.

Methods: Patients received a physical examination, and blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the candidate genes: gammaC-crystallin (CRYGC), gammaD-crystallin (CRYGD), gammaS-crystallin (CRYGS), gap-junction protein, alpha 8 (GJA8), gap-junction protein, alpha 3 (GJA3), and alphaA-crystallin (CRYAA).

Results: The affected individuals in two families had congenital coralliform cataracts. Mutational analysis of the CRYGD identified a C→A transversion at nucleotide position c.70 in exon 2, which resulted in a threonine substitution for proline at amino-acid residue 24 (P24T). This mutation was identified in all affected individuals but was not found in healthy relatives or 100 control chromosomes from the same ethnic background.

Conclusions: Our results indicated that the P24T mutation of CRYGD was responsible for two Chinese pedigrees with congenital coralliform cataracts. CRYGD and coralliform cataracts are highly related, and P24T may be a hot-point mutation for this disorder.

Figure 1

Pedigree and haplotype. Haplotype analysis of the families demonstrated segregation of three microsatellite markers flanking CRYGD on chromosome 2q33-q35 region.

Figure 2

Slit lamp photograph showing coralliform cataract of patient: II:6 in family 1 and III:7 in family 2 (from Figure 1).

Figure 3

DNA sequences of CRYGD in unaffected and affected individuals. The C→A transversion resulted in a threonine substitution for proline at amino-acid residue 24 (P24T) in the affected individuals.