一例火棉胶婴儿TGM1基因新的复合杂合性突变鉴定  

Novel compound heterozygous mutations of TGM1 gene identified in a Chinese collodion baby

作　　者：张永玲[1] 岳智慧[1] 袁萍[1] 周庆[1] 黄玮俊[1] 胡彬[1] 王一鸣[1] 

机构地区：[1]中山大学中山医学院医学遗传学教研室疾病基因组研究中心张永玲、袁萍、黄玮俊、胡彬、王一鸣,第一附属医院儿科（岳智慧）；江西于都县人民医院儿科（周庆）,广州510080

出　　处：《中华医学遗传学杂志》2012年第1期1-4,共4页Chinese Journal of Medical Genetics

基　　金：广东省自然科学基金（10151008901000003）;教育部新教师专项基金（20100171120055）;广州市科技计划项目（2010J-E191）;中山大学校内基金（10ykjc07）

摘　　要：目的鉴定1例火棉胶婴儿转谷氨酰胺酶1基因（transglutaminase1，TGM1）的致病性突变。方法提取患儿及其父母的外周血DNA，PCR扩增TGM1基因的编码及剪切位点序列，对PCR产物进行直接测序。同时检测i00名无血缘关系的正常人作为对照。用TGMl邻近的微卫星标记在家系中构建单倍型以确定突变的来源。应用CLUSTALx（1．81）软件分析突变氨基酸的跨种属保守性。结果患儿携带了TGMl的两个复合杂合性突变：c．420A〉G（1140M）及C．832G〉A（G278R），均为国际上未报道过的新突变。两个错义突变均造成了TGM1蛋白内高度保守区的氨基酸置换。突变C．420A〉G（1140M）遗传自父亲，位于蛋白的转谷氨酰胺酶N功能域；突变c．832G〉A（G278R）遗传自母亲，位于野生蛋白的转谷氨酰胺酶N功能域和转谷氨酰胺酶样功能域之间。两个突变在100名无血缘关系的正常人中均未发现。结论c．420A〉G（1140M）和C．832G〉A（G278R）复合杂合性突变为该患儿的致病性突变，本研究结果为该病的诊断提供了分子学依据。Objective To identify potential mutations in a Chinese collodion baby. Methods The patient was investigated clinically. DNA was extracted from peripheral blood of the baby and his parents. All coding exons （exons 2-15） and splicing sites of transglutaminase 1 （TGM1） were amplified by polymerase chain reaction （PCR）. Mutation detection was performed by directed sequencing of the PCR products. A total of 100 healthy unrelated subjects were used as controls. Haplotypes were constructed with microsatellites flanking the locus, and TGM1 genotypes of the family were used to determine parental origins of the mutations. CLUSTAL X （1.81） was employed to analyze cross-species conservation of the mutant protein sequence. Results The boy was found to be a compound heterozygote for two novel mutations., c. 420A：〉G （I140M） from his father and c. 832G^A （G278R） from his mother, with the former occurring in the transglutaminase N domain and the latter between transglutaminase N and transglutaminase-like domains. Both mutations were absent from the control subjects. Conclusion The boy＇s condition was caused by two novel compound heterozygous mutations of c. 420A〉G and c. 832G〉A of TGM1 . Author＇s results may provide new clues for molecular diagnosis of this disease.

关 键 词：TGM1基因 复合杂合性突变 火棉胶婴儿 

分 类 号：R758.52[医药卫生—皮肤病学与性病学]