常染色体显性遗传先天性核性白内障一家系致病基因的初步定位

Initial gene mapping of a pedigree with autosomal dominant congenital nuclear cataract

目的 初步定位一个显性遗传性先天性核性白内障家系的致病基因.方法 在已知与先天性白内障相关的致病基因附近选择合适的微卫星标记,基因组PCR扩增后进行基因分型,由LINKAGE软件处理,对该家系进行连锁分析.结果 在22q的D22S258、D22S315、D22S1163显示最大LOD值2.11（重组率θ=0）.单倍型分析提示致病基因位于D22S1174～D22S270大约18.5 Mbp的遗传距离.结论 该家系的致病基因定位于22q11.2～22q13,该范围内的CRYBB1、CRYBB2、CRYBB3、CRYBA4为其可能致病基因.

Objective To initial map the gene for autosomal dominant congenital nuclear cataract in a four generation pedigree. Methods Blood sampies were collected from 12 members of this family. Linkage analysis was performed with microsatellite markers closed to 17 loci previously reported to be associated with cataract. Results The maximum LOD score （ Zmax= 2.11 at recombination fraction θ = 0 ） was obtained for markers D22S258、 D22S315、 D22S1163. The analysis of haplotype indicated the affected haplotype was located from D22S1174 to D228270 with a genetic distance of 18.5 Mbp. Conclusion The mutation gene in this pedigree is located at chromosome 22q11. 2 - 22q13. This result will be helpful for identifying the genetic default in this pedigree and further studying the pathogenesis of cataract.