Abstract

Background: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common.

Objective: To report the identification of a mutation in the human CRYGS gene.

Subjects and methods: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out.

Results: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (θ = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G→T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011).

Conclusions: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.