A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family.
OBJECTIVE
To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family.


METHODS
Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant gammaC-crystallin were generated and analyzed by SWISS-MODEL.


RESULTS
Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated gammaC-crystallin.


CONCLUSIONS
A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.
Yao
Ke
K
Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China. xlren@zju.edu.cn
Jin
Chongfei
C
Zhu
Ning
N
Wang
Wei
W
Wu
Renyi
R
Jiang
Jin
J
Shentu
Xingchao
X
D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002681:China; D018389:Codon, Nonsense / Q000235:genetics*; 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; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D010375:Pedigree; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D038222:gamma-Crystallins / Q000737:chemistry / Q000235:genetics*
D018389:Codon, Nonsense; C522806:Crygc protein, human; D050505:Mutant Proteins; D038222:gamma-Crystallins