Congenital polymorphic cataract associated with a G to A splice site mutation in the human beta-crystallin gene CRYβA3/A1.
OBJECTIVE
To identify the underlying genetic defect in four generations of a Chinese family affected with bilateral congenital polymorphic cataracts.


METHODS
Family history and clinical data were recorded. The phenotype was documented using slit-lamp photography. Genomic DNA samples were extracted from peripheral blood of family members. Candidate genes were amplified using polymerase chain reaction (PCR) and screened for mutations on both strands using bidirectional sequencing.


RESULTS
Affected individuals exhibited variable opacities in the embryonic nucleus, sutures, and peripheral cortical opacities. The phenotype for this family was identified as polymorphic. Direct sequencing revealed a splice site mutation (c.215+1G>A) at the first base of intron 3 of the crystallin beta A3/A1 (CRYBA3/A1) gene. This mutation co-segregated with all affected individuals in the family and was not found in unaffected family members or in 100 unrelated controls.


CONCLUSIONS
Our results identified a recurrent c.215+1G>A mutation in CRYBA3/A1 in a polymorphic congenital cataract family, summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of congenital cataract in a different ethnic background, and suggested a mechanism that influences cataractogenesis.
Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
Yibo
Y
Yu
Jinyu
J
Li
Jia
J
Xu
Qiwei
Q
Wang
Yinhui
Y
Yu
Ke
K
Yao
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics*; D017422:Sequence Analysis, DNA; D038205:beta-Crystallin A Chain / Q000235:genetics*
C489108:CRYBA1 protein, human; D022821:RNA Splice Sites; D038205:beta-Crystallin A Chain