Reis-Bücklers角膜营养不良患者TGFBI基因突变  

Analysis of gene mutation in Chinese patients with Reis-Bücklers corneal dystrophy

作　　者：田欣[1] 刘祖国[2] 李勤[3] 李冰[4] 王薇[1] 谢培英[5] 藤木庆子 村上晶 金井淳 

机构地区：[1]北京大学眼科中心,100083 [2]中山大学中山眼科中心 [3]吉林大学中日联谊医院眼科 [4]山西省眼科医院 [5]北京大学眼视光学研究中心 [6]日本顺天堂大学眼科

出　　处：《中华眼科杂志》2005年第3期239-242,共4页Chinese Journal of Ophthalmology

基　　金：留学归国人员启动基金资助项目 ( 2002 );国家杰出青年科学基金资助项目(30225044)

摘　　要：目的　探讨中国Reis Bücklers角膜营养不良患者的TGFBI基因的突变特征及其与临床表现的关系。方法　对于彼此无亲缘关系的两家系 10例患者及其家族中 2名正常成员进行基因分析。采取外周血 10ml,制备外周血白细胞基因组DNA,应用合成的特异性引物,聚合酶链反应(PCR)分别扩增TGFBI基因的第 4、12外显子,将基因产物进行直接测序,分析相应基因序列。结果两家系均呈现常染色体显性遗传。临床上表现为角膜上皮下及前弹力膜中细小的颗粒状混浊,随年龄增长而逐渐融合、扩大呈地图样外观,符合Reis Bücklers角膜营养不良地图型的诊断。基因序列分析呈现TGFBI基因第 124密码子第二个碱基G→T碱基点突变,导致精氨酸转变为亮氨酸(R124L)。结论　中国Reis Bücklers角膜营养不良患者两家系均呈现R124L基因突变,表现为Reis Bücklers角膜营养不良地图型改变。基因分析将为疾病的确诊提供可靠依据。Objective To identify the mutation of the TGFBI gene in Chinese patients with Reis Bücklers corneal dystrophy, and to study the relationship between the gene mutation and the clinical appearance Methods Ten patients and 2 unaffected family members from 2 unrelated families with corneal dystrophy were studied Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes, and exons 4 and 12 of the TGFBI gene were amplified by polymerase chain reaction for direct sequencing Results Both pedigrees showed an autosomal dominant inheritance The clinical appearance of the cornea consisted of fine granular, subepithelial opacities which spread and become confluent with time, and resembled geographic type of Reis Bücklers corneal dystrophy Direct sequencing of all affected members revealed a G to T transition at codon 124 (CGC to CTC), producing R124L mutation of TGFBI gene Conclusions R124L mutation of the TGFBI gene is found in two Chinese families with Reis Bücklers corneal dystrophy The phenotype of Reis Bücklers corneal dystrophy in both families belongs to the geographic type Molecular genetic approach may be useful for the proper diagnosis of this type of corneal dystrophy

关 键 词：角膜营养不良 患者 家系 基因突变 诊断 基因分析 年龄增长 地图 弹力 结论 

分 类 号：R772.2[医药卫生—眼科] R735[医药卫生—临床医学]