Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.
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.


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 (theta = 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.
Sun
H
H
Eye Centre of Tianjin Medical University, Tianjin, China.
Ma
Z
Z
Li
Y
Y
Liu
B
B
Li
Z
Z
Ding
X
X
Gao
Y
Y
Ma
W
W
Tang
X
X
Li
X
X
Shen
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D005190:Family; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016415:Sequence Alignment; D038222:gamma-Crystallins / Q000235:genetics*
D038222:gamma-Crystallins; C077648:CRYGS protein, human