常染色体显性遗传先天性板层白内障家系致病基因的排除性定位

目的 定位-个四代常染色体显性遗传先天性板层白内障家系的致病基因.方法 选取在北京同仁医院就诊的河北任丘先天性白内障家系,记录家系遗传史.该家系28例成员(12例患者,16例非患者)进入本研究,12例患者接受全身及眼部检查,以排除存在白内障以外的眼部及全身疾患,16例非患者仅接受眼部检查.28例研究对象均采集外周静脉血5ml,提取基因组DNA,选取在物理距离上与已知非综合征常染色体显性遗传性先天性白内障相关的18个致病基因紧密连锁的微卫星分子标记,基因组聚合酶链式反应(PCR)扩增后进行基因分型.以基因分型的结果为基础,利用等位基因共享分析和基因测序对已知候选基因进行排除定位.结果 该家系遗传特点符合常染色体显性遗传,临床表型为板层先天性白内障;与位于1、2、10、11、12、16、17、21、22染色体上的15个致病基因附近的微卫星位点均不存在等位基因共享,基因测序排除了微卫星杂合度较低(位于3、13,19号染色体)的基因座.结论 该家系存在新的致病基因,进一步确证了先天性白内障具有高度临床和遗传异质性.该家系致病位点的确定有待于进一步研究.

Exclusive mapping of all known locus linked with autosomal dominant congenital lamellar cataract in a Chinese family

Objective To map the mutation gene of autosomal dominant congenital lamellar cataract in a family pedigree of four generations.Methods A Family with non-syndromic congenital cataract was recruited from the Eye Center of Tongren Hospital affiliated to Capital Medical University.Family history was recorded.Twenty-eight members of the family pedigree(including twelve affected and sixteen unaffected individuals)were enrolled into the study with informed consent.The twelve affected individuals underwent full clinical and ophthalmological examinations to rule out any concomitant disorders.The sixteen unaffected individuals only underwent ophthalmological examination.Blood samples were collected from all the 28 subjects for genomic DNA preparation.Eighteen different genes were previously reported to be associated with non-syndromic autosomal dominant congenital cataract(ADCC).Multiplex polymerase chain reaction(PCR)was carried out with microsatellite markers near to candidate loci related to congenital cataracts.PCR products from each DNA sample were separated on a 6% polyarcylamide gel and analyzed.Exclusion analysis was performed by allele sharing analysis and gene sequencing.Results The clinical phenotype in the family was isolated corroborating autosomal dominant congenital lamellar cataract.No mutation was found in the eighteen genes in all twenty-eight subjects.Eighteen candidate genes were excluded by allele sharing method and gene sequencing.Conclusion All known ADCC loci have been excluded from this family,which further indicates the clinical and genetical heterogeneity of congenital cataract,and an important clue is provided for finding more cataract responsible genes.Further study should be carried out to screen other relevant genes or loci in patients with ADCC.