东北地区一遗传性白内障家系的临床遗传学及基因定位研究

目的:分析一先天性核型白内障家系的遗传方式及致病基因所在位置。方法:收集一个3代遗传性白内障家系成员的临床资料;提取家系成员外周血DNA,选取62个态性微卫星标记进行连锁分析。应用LINKAGE软件(version 5.2)中的MLINK程序计算两点连锁LOD值,并人工构建家系成员的单体型。结果:确定该家系为一常染色体显性遗传性白内障大家系,在微卫星标记D22S689可获得最大LOD值2.71(θ=0时),单体型提示该家系表型可能与染色体22q11.2-12.1区域连锁。该区域含有CRYBB1,CRYBB2,CRYBB3,CRYBA44个候选基因。结论:本研究先天性核型白内障家系符合常染色体显性遗传规律,其致病基因定位于22q11.2-12.1区域。

Clinical genetics and gene mapping studies on a family in the area of northeast with hereditary cataract

AIM： To map the causal gene of congenital nuclear cataract in a family in the area of northeast. METHODS： We investigated there generations of a Chinese family affected with hereditary cataract. Peripheral blood samples were collected from all of the family members, and genomic DNA was then extracted from the blood samples. Linkage analysis was performed using 62microsatellite markers. Two-point LOD scores （Z） were calculated using the LINKAGE programs （ver. 5. 2）. Haplotypes were constructed according to the allele information. RESULTS ： The affected members in this family showedclassic phenotype of autosomal dominant congenital cataract. The maximum two- point LOD score of 2.71 was obtained for marker D22S689 （θ = 0）. Haplotype analysis traced the disease gene on chromosome 22q11.2- 12.1, containing CRYBB1, CRYBB2, CRYBB3, CRYBA4 genes. CONCLUSION： The occurrence of congenital nuclear cataract consistents with the autosomal dominant inherited regular, and the causal gene of congenital nuclear cataract localize at 22q11.2-12.1 in this family.