A deletion mutation in the betaA1/A3 crystallin gene ( CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family.
Congenital cataracts are an important cause of blindness worldwide. In a family of Chinese descent, a dominant congenital nuclear cataract locus was mapped to chromosome 17q11.1-12. The maximum LOD score, 2.49, at recombination fraction 0, was obtained for marker D17S1294. The results of both linkage and haplotype analyses defined a disease-gene to an 11.78-cM region harboring the gene coding for betaA1/A3 crystallin ( CRYBA1/A3). Mutation analysis of the CRYBA1/A3 gene identified a 3-bp deletion in exon 4, which cosegregated with the disease risk in this family and was not observed in 100 normal chromosomes. This mutation resulted in the deletion of a highly conserved glycine at codon 91 (DeltaG91) and could be associated with an incorrect folding of betaA1/A3 crystallin. It highlights the physiological importance of crystallin and supports the role of CRYBA1/A3 in human cataracts formation.
Qi
Yanhua
Y
Department of Ophthalmology, The Second Affiliated Hospital, Haerbin Medical University, Haerbin, 150086 Heilongjiang, P.R. China. qi_yanhua@yahoo.com
Jia
Hongyan
H
Huang
Shangzhi
S
Lin
Hui
H
Gu
Jingzhi
J
Su
Hong
H
Zhang
Tieying
T
Gao
Ya
Y
Qu
Lijun
L
Li
Dandan
D
Li
Ying
Y
D000595:Amino Acid Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002681:China; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003459:Crystallins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D038205:beta-Crystallin A Chain
C489108:CRYBA1 protein, human; D003459:Crystallins; D017931:DNA Primers; D005819:Genetic Markers; D038205:beta-Crystallin A Chain