摘要背景 研究发现角膜营养不良与位于染色体5q31区域转化生长因子β诱导基因(TGFBI)的突变有关,目前发现Avellino角膜营养不良的TGFBI基因突变位点为R124H.目的 检测中国遗传性Avellino角膜营养不良一家系的致病基因并进行分子遗传学分析,探讨其TGFBI的基因突变类型.方法 本家系先证者在北京大学第三医院确诊,共调查连续4代27名成员,收集遗传性Avellino角膜营养不良患者8例和表型正常成员2名的外周血3 ml提取DNA,合成TGFBI第4、11、12外显子的特异性引物,采用聚合酶链反应(PCR)进行扩增,对PCR产物直接进行DNA测序分析并与正常GenBank中的TGFBI基因序列比对.结果 该家系中Avellino角膜营养不良的遗传模式符合常染色体显性遗传,8例患者的TGFBI基因第4外显子均显示CGC>CAC(R124H)突变杂合子,家系中的2名表型正常成员无此基因位点突变.8名家系成员存在第11外显子的472密码子CTC>CTT的杂合性同义单核苷酸多态性(SNP),9名家系成员存在第12外显子的540密码子TTT>TTC的杂合性同义SNP,且SNP与疾病表现型无关.结论该Avellino角膜营养不良家系存在TGFBI基因突变,为R124H杂合突变类型.

abstractsBackground Researches demonstrated that corneal dystrophy is associated with the mutation of transforming growth factor beta induced gene(TGFBI)located at chromosome 5q31 domine.Recent study showed that the gene mutation location is in R124H of TGFBI gene. Objective This study was to identify the mutation characteristics of TGFBI gene in a Chinese family with Avellino corneal dystrophy. Methods This Chinese family with Avellino corneal dystrophy were determined and surveyed in Peking University Third Hospital.Periphery blood from 8 patients with Avellino corneal dystrophy and 2 unaffected subjects were collected from a Chinese family with corneal dystrophy for the extraction of DNA.Exons 4,11,12 of the TGFBI gene were amplified by polymerase chain reaction(PCR),and the amplified products were sequenced directly and compared the gene sequence with that of TGFBI in GenBank.Written informed consent was obtained from each Subject prior to any medieal process. Results This family included 27 members of consecutive 4 generation.The hereditary pattern W88 in accordance with the autosomal dominant inheritance.Directly sequencing of 8 affected members revealed a G tO A transition at codon 124 (CGC to CAC),producing R124H mutation of TGFBI gene.Two synonymous single nucleotide polymorphism(SNP)of TGFBI gene occurred in the family.including a C to T transition at eodon 472(CTC to CTT)in 8 members,and a T to C transition at codon 540(TTT>TTC)in 9 members,which wag unrelated with disease. Conclusion R124H mutation of the TGFBI gene is found in this Chinese family with Avellino corneal dystrophy.