A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract.
BACKGROUND
Congenital cataract is a highly heterogeneous disorder at both the genetic and phenotypic levels. This study was conducted to identify disease locus for autosomal dominant congenital cataracts in a four generation Chinese family.


METHODS
Family history and clinical data were recorded. All the members were genotyped with microsatellite markers which are close to the known genetic loci for autosomal congenital cataracts. Two-point Lod scores were obtained using the MLINK of the LINKAGE program package (ver 5.1). Candidate genes were amplified by polymerase chain reaction (PCR) and direct cycle sequencing.


RESULTS
The maximum Lod score of Zmax-2.11 was obtained with three microsatellite markers D22S258, D22S315, and D22S1163 at recombination fraction theta=0. Haplotype analysis showed that the disease gene was localized to a 18.5 Mbp region on chromosome 22 flanked by markers D22S1174 and D22S270, spanning the beta-crystallin gene cluster. A c.752T-->C mutation in exon 6 of CRYBB1 gene, which resulted in a heterozygous S228P mutation in predicted protein, was found to cosegregate with cataract in the family.


CONCLUSIONS
This study identified a novel mutation in CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract. These results provide strong evidence that CRYBB1 is a pathogenic gene for congenital cataract.
Wang
Jun
J
Beijing Tongren Eye Center, Capital Medical University, Beijing 100730, China.
Ma
Xu
X
Gu
Feng
F
Liu
Ning-pu
NP
Hao
Xiao-lin
XL
Wang
Kai-jie
KJ
Wang
Ning-li
NL
Zhu
Si-quan
SQ
D000595:Amino Acid Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D038206:beta-Crystallin B Chain / Q000235:genetics*
D038206:beta-Crystallin B Chain