一常染色体显性遗传性白内障家系致病基因的排除性定位

目的对常染色体显性遗传先天性白内障家系进行致病基因的定位研究。方法对4代11例家系成员（6例患者）进行眼部和全身检查,采集静脉血,提取基因组DNA,选取已报道的与遗传性白内障相关位点附近的微卫星标记,PCR扩增后进行基因型分析,用连锁分析进行排除;没有排除的位点,基因外显子测序。结果 35例家系成员中,追溯调查共有10例患者,其中第1代1例,第2代2例,第3代5例,第4代2例。该家系患者表型为完全性白内障;绝大多数位点,患者没有共享基因型;微卫星标记与致病基因间的2点连锁Lod值〈-2,证实这些位点与该家系的致病基因不连锁;有3个多态性标记（D10S1239、D22S286、D22S926）0〈Lod值≤0.6,Lod值虽然不是〈-2,但在家系患者中没有共享等位基因;测序未发现外显子有突变。结论此家系的致病基因不是已报道位点的致病基因,其致病基因有待进一步研究。

Exclusive mapping for all known loci in a family with congenital Cataract

Background Congenital cataract include three types inhereet fashion,and autosomal dominant congenital cataract （ADCC） is most common.It is known that 21 genes participate in the pathogenesis of congenital cataract.Objective This study aimed to map the pathogenic gene in a four-generation family with autosomal dominant congenital cataract.Methods Eleven members of the family,including six affected and five unaffected individuals,were enrolled into the study.The eleven individuals underwent full ophthalmological and clinical examinations to rule out any concomitant disorders.Blood samples were collected from all the 11 subjects for genomic DNA preparation.Microsatellite markers which near the reported loci and associated with congenital cataract were selected.Each DNA sample was amplified using polymerase chain reactions （PCR）.Then the PCR products were separated and analyzed by polyacrylamide gel electrophoresis.Exclusion analysis was performed by linkage analysis.If the locus cannot be excluded by linkage analysis,the candidate gene was sequenced.This study followed the Hersinki Declation and was approved by Ethic Committee of this hospital.All of the subjects read and signed the informed consent sheet.Results In total 35 members,10 patients were determined,including 1 patient in the first generation,2 patients in the second generation,5 patients in third genetation and 2 patients in the forth generation.The phenotype of the families was entire cataract.The Lod scores were〈 -2 in most of the polymorphic microsatellite markers.indicating that there was no linkage between these microsatellite markers and congenital cataract related genes in this family.The Lod score of three markers （D10S1239,D22S286,D22S926） although not〈 -2,but all patients did not have the same allele.Gene sequencing did not found mutation.Conclusion The pathogenic gene in this congenital cataract family is not located on 16 known chromosome loci.Further genetic study is needed to this special family.