A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family.
OBJECTIVE
To identify the genetic defects associated with autosomal dominant congenital nuclear cataract in a Chinese family.


METHODS
Clinical data were collected, and the phenotypes of the affected members in this family were recorded by slit-lamp photography. Genomic DNA was isolated from peripheral blood. Mutations were screened in cataract-associated candidate genes through polymerase chain reaction (PCR) analyses and sequencing. Structural models of the wild-type and mutant alphaB-crystallin were generated and analyzed by SWISS-MODEL.


RESULTS
Mutation screening identified only one heterozygous G-->A transition at nucleotide 32 in the first exon of alphaB-crystallin (CRYAB), resulting in an amino acid change from arginine to histidine at codon 11 (R11H). This mutation segregated in all available affected family members but was not observed in any of the unaffected persons of the family. The putative mutation disrupted a restriction site for the enzyme, Fnu4HI, in the affected family members. The disruption, however, was not found in any of the randomly selected ophthalmologically normal individuals or in 40 unrelated senile cataract patients. Computer-assisted prediction suggested that this mutation affected the biochemical properties as well as the structure of alphaB-crystallin.


CONCLUSIONS
These results supported the idea that the novel R11H mutation was responsible for the autosomal dominant nuclear congenital cataract in this pedigree.
Chen
Qiang
Q
Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, China.
Ma
Junjie
J
Yan
Ming
M
Mothobi
Maneo Emily
ME
Liu
Yuanyuan
Y
Zheng
Fang
F
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017433:Protein Structure, Secondary; D038203:alpha-Crystallin B Chain / Q000737:chemistry / Q000235:genetics*
C059215:CRYAB protein, human; D038203:alpha-Crystallin B Chain