一个致密核性先天性白内障家系致病基因的初步研究  

Gene mapping of a congenital nuclear cataract in a Chinese family

作　　者：郝晓琳[1] 马旭[2] 谷峰[2] 唐思梦[1] 王俊[1] 王开杰[1] 朱思泉[1] 

机构地区：[1]首都医科大学附属北京同仁医院眼科中心,北京100730 [2]国家人口计生委科学技术研究所

出　　处：《解放军医学杂志》2007年第6期552-554,564,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金资助项目(30471864);国家科技部重点项目(2003DEA3N026)

摘　　要：目的对一个致密核性先天性白内障家系的致病基因进行定位。方法根据已报道的与先天性白内障相关基因的位置,选择紧密连锁的微卫星多态性标记,PCR扩增后进行基因分型,以分型结果为基础,利用等位基因共享分析和两点连锁分析对已知候选基因进行排除定位。结果该家系临床表型为致密核性先天性白内障,目前尚无关于该表型致病突变的报道。已知的15个候选基因区域附近的微卫星位点均不存在等位基因共享;除D11S898外,其余27个微卫星位点的LOD值在重组率(θ)为0时均为-∝,致病基因与15个已知基因之间不存在连锁关系。结论该家系的致病基因不是15个已知的先天性白内障相关基因,其致病基因有待进一步研究。Objective Mapping the responsible gene for congenital nuclear cataract in a family for five generations in Yantai City, Shandong Province, China. Methods Family history and clinical data were recorded. 9 unaffected members and 13 affected members in this family were involved in the study. The genes of all the involved members were amplified by polymerase chain reaction （PCR）. 28 microsatellite polymorphism in the 15 reported disease loci were used as genetic markers. The PCR products from each DNA sample were separated on a 6% polyaerylamide gel and analyzed. Allele-sharing analysis was carried out for exclusion, and linkage analysis was calculated with the LINKAGE （Version 5. 1） package. Direct sequencing was used for GJA3 gene. Results The clinical phenotype in this family was isolated congenital nuclear cataract, the pathogenic nutation of the phenotype of which has not been reported yet. For all the 28 markers around the 15 candidate loci, there was no allele-sharing between the affected family members. At the 0. 00 recombination frequency, the LOD score was -oc in 27 of the 28 microsatellite markers with exception of DllS898. No GJA3 gene mutation was found. It indicated that there was no linkage between these markers and the pathogenic gene in this family. Conclusion The responsible gene for the congenital nuclear cataract in this family is not located on the 15 reported loci, which further indicates the clinically and genetically heterogeneity of inherited cataract, and an important clue is provided for finding more cataract responsible genes. The pathogenic gene in this family should be identified through extensive scanning of genes.

关 键 词：白内障 先天性 微卫星重复 等位基因 连锁分析 

分 类 号：R776.1[医药卫生—眼科]