Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family.
OBJECTIVE
A four-generation Chinese family with 13 members affected with autosomal dominant congenital posterior polar cataract was studied. The purpose of this study was to identify the disease-causing gene in the family and to validate that mutations in CRYAB, the alphaB-crystallin gene, cause the congenital cataract.


METHODS
Linkage analysis was performed with a panel of microsatellite markers flanking candidate genetic loci for cataracts, including 14 known autosomal dominant congenital cataract (ADCC) genes. For mutation analysis, the complete coding region and exon-intron boundaries of CRYAB were sequenced with DNA from the proband. Single-strand conformation polymorphism (SSCP) analysis for exon 1 of CRYAB was performed in all family members and 200 normal control subjects.


RESULTS
The disease gene in the Chinese family was mapped to chromosome 11 in region q22-22.3 with a maximum lod score of 4.52. Direct DNA sequence of CRYAB revealed a heterozygous C-->T transition at nucleotide 58, resulting in a novel 58 C-->T (Pro20Ser) mutation. The Pro20Ser mutation cosegregated with all affected individuals and was not present in unaffected members in the family or in 200 normal control subjects. The mutation occurs at the evolutionarily conserved residue Pro20 in the N-terminal region of alphaB-crystallin.


CONCLUSIONS
To date, only one CRYAB mutation has been associated with congenital isolated cataract. This study identified a second novel mutation in CRYAB in a large Chinese cataract family. Together, these results provide strong evidence that CRYAB is a pathogenic gene for congenital cataract.
Liu
Mugen
M
Center for Human Genome Research and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, Peoples Republic of China.
Ke
Tie
T
Wang
Zhaoxiang
Z
Yang
Qinbo
Q
Chang
Wei
W
Jiang
Fagang
F
Tang
Zhaohui
Z
Li
Hui
H
Ren
Xiang
X
Wang
Xu
X
Wang
Tao
T
Li
Qingchun
Q
Yang
Junguo
J
Liu
Jingyu
J
Wang
Qing Kenneth
QK
D000368:Aged; D044466:Asian People / Q000208:ethnology; D002386:Cataract / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D038203:alpha-Crystallin B Chain / Q000235:genetics*
C059215:CRYAB protein, human; D038203:alpha-Crystallin B Chain