目的:对一个4代常染色体显性遗传先天性白内障家系进行致病基因研究。方法:对15例家系成员(8例患者,7例非患者)进行眼部检查,采集静脉血,提取基因组DNA,选取已报道的与常染色体显性遗传性白内障相关的19个位点附近的微卫星标记,PCR扩增后进行基因型分析,用连锁分析进行定位;对提示连锁的标记计算Lod值,并构建单体型;对定位区域内已知候选基因测序。结果:该家系患者表型为绕核性白内障;患者在17q11-12有共享基因型,该位点微卫星标记与致病基因间的两点连锁最大Lod值为2.71,证实该位点与该家系的致病基因连锁;测序未发现CRYBA1/BA3突变。结论:该家系的致病突变不是由于CRYBA1/A3外显子和调控区突变,可能是未被发现基因突变或机制参与该家系的发病。

AIM:To detect the pathogenic gene in a four-generation family with autosomal dominant congenital cataract.METHODS:Fifteen members of the family(including eight affected and seven unaffected individuals)were enrolled into the study.The fifteen individuals underwent full ophthalmological and clinical examinations to rule out any concomitant disorders.Blood samples were collected from all the 15 subjects for genomic DNA preparation.Microsatellite markers which were near the reported loci to be associated with autosomal dominant congenital cataract were selected,and amplified from each DNA sample using polymerase chain reactions(PCR).Then the PCR products were separated and analyzed by polyacrylamide gel electrophoresis.Location analysis was performed by linkage analysis,Lod scores of possibly linkaged markers were calculated.According to the allele and the relation between family members,the family haplotype was constructed artificially.For the ascertained domain in the chromatosome,gene sequencing was performed to identify the mutation.RESULTS:The phenotype of the family is perinuclear cataract.The Lod scores were 2.71 in the polymorphic microsatellite markers on 17q11-12 and all the affected had the same allele,indicating that there was linkage between these microsatellite markers and congenital cataract related genes in this family.Gene sequencing did not found CRYBA1/A3 mutation.CONCLUSION:The pathogenic mutation is not caused by the mutation of the exons and untranslated region in CRYBA1/A3.There may be other gene mutation or mechanism leading to the morbility of this autosomal dominant congenital cataract.

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中国国家自然科学基金资助项目(No.30973276);中国辽宁省科技厅科学计划基金资助项目(No.2008408002-1)~~