Two Chinese families with pulverulent congenital cataracts andΔG91 CRYBA1 mutations

[摘要] Purpose: To characterize the disease-causing mutations and relatedphenotypes in two Chinese families with autosomal dominant congenitalcataract.Methods: Family members were clinically characterized by a completeeye examination. Genome-wide linkage screening was performed in Family 1using a 10K single nucleotide polymorphism approach followed bygenotyping of microsatellite markers from the regions with highestsupport for linkage. The candidate gene, βA1-crystallin(CRYBA1), was sequenced in both families.Results: Lens examinations in three affected phakic members showedbilateral pulverulent nuclear cataracts in two subjects of Family 1while another subject of Family 2 displayed bilateral pulverulentlamellar cataract. Linkage analysis in 14 individuals (eight affected,three unaffected and three of their spouses) of Family 1 gave a maximumlogarithm of odds score of 2.41 for D17S1294 in chromosomal region17q11.12 that includes the CRYBA1 gene. In both families in-framedeletions of three bp were detected in exon 4 of CRYBA1 leading toloss of a guanine residue (ΔG91). The mutations cosegregatedcompletely with the cataract phenotype in both families but wereassociated with distinct haplotypes suggesting that they had occurredindependently.Conclusions: The previously described CRYBA1 mutation ΔG91was demonstrated in two Chinese families with distinct phenotypes ofcongenital cataract, suggesting a lack of genotype-phenotypecorrelation. The findings also raise the possibility that the ΔG91mutation arise in a relatively mutation-prone sequence of the CRYBA1gene.

[学科分类] 生物化学/生物物理