火棉胶样儿的基因突变分析一例  

Gene mutation analysis of a collodion baby

作　　者：佃艳[1] 孟岩[1] 王铮[1] 彭园园[1] 周青[1] 李晓侨[1] 苏亮[1] 黄尚志[1] 

机构地区：[1]中国医学科学院基础医学研究所医学遗传学系北京协和医学院基础学院WHO遗传病社区控制合作中心(中国北京),100005

出　　处：《中华儿科杂志》2009年第9期654-657,共4页Chinese Journal of Pediatrics

基　　金：基金项目：北京市科学技术委员会研发攻关项目（D0906005040491）;“十一五”国家科技支撑计划项目（2006BA105A08）

摘　　要：目的确定1例火棉胶样儿的基因突变。方法火棉胶样儿所涉及的突变基因很多，分析患儿临床表现后，依文献报道，选择突变发生率最高的基因——转谷丙酰胺酶基因1（TGM1）作为候选基因，采用PCR方法对TGM1基因的所有外显子及其旁侧内含子序列进行扩增，并进行PCR产物正反向直接测序。对错义突变设计等位基因特异性PCR引物，进行群体检验。结果患儿TGM1基因存在3个新的异常：外显子3中c．463C〉T点突变，导致错义突变P．Arg155Trp；外显子4中缺失G（c．694delG），导致移码突变P．Glu232SeffsX98；外显子4中存在另1个c．578G〉A点突变，导致无义突变P．Trp193X。其父亲为c．694delG突变杂合子，母亲则为具有c．463C〉T、c．578G〉A双重突变的杂合子。c．463C〉T等位基因特异性PCR（AS—PCR）群体检验结果显示，正常对照人群中没有此突变。结论该火棉胶样儿由TGM1基因突变引起，存在3种致病突变，其中两个突变（c．463C〉T／c．578G〉A）发生在母源等位基因，而另一个突变来源于父亲。Objective To determine the mutations pattern of the genes of a collodion baby. Methods Collodion baby is a genetic heterogeneous disease caused by mutations of several genes. Since the most common mutations were observed in TGM1 gene, this gene was chosen for mutation screening. The screening was carried out by PCR and direct sequencing. The allele specific primers were designed for a missense mutation and allele-specific （AS） PCR was carried out in 50 normal individuals for population study. Results Three novel alterations were detected in TGMI gene of the proband, a missense mutation c.463C 〉T （p. Arg155Trp） in exon 3, a nonsense mutation c. 578G 〉 A （p. Trp193X） in exon 4, and a single nucleotide deletion （c. 694delG） also in exon 4 of TGMI geue. This infant＇s father was heterozygote of c. 694delG mutation, while his mother carried the two mutations （ c. 463C 〉 T and c. 578G 〉 A） on the same chromosome. The missense mutation was not detected in his father and in any of the control individuals by AS-PCR. Conclusion Three novel mutations were identified in TGMlgene in a Chinese collodion baby. A double mutation （ c. 463C 〉 T and c. 578G 〉 A ） located on the maternal allele while the c. 694delG deletion on the paternal allele.

关 键 词：遗传性疾病 先天性 基因 隐性 突变 火棉胶样儿 

分 类 号：R686[医药卫生—骨科学]