학술논문
一种新的复合杂合突变导致3-甲基巴豆酰辅酶A羧化酶缺乏症 / A novel compound heterozygous mutation causing 3-methylcrotonyl-CoA carboxylase deficiency
Document Type
Academic Journal
Author
谢波波; 罗静思; 雷亚琴; 陈荣誉; 王锦; 张淑杰; 范歆; 李旺; 陈少科; Xie Bobo; Luo Jingsi; Lei Yaqin; Chen Rongyu; Wang Jin; Zhang ShuJie; Fan Xin; Li Wang; Chen Shaoke
Source
中华医学遗传学杂志. 33(5):657-661
Subject
Language
Chinese
ISSN
1003-9406
Abstract
目的：对1例新生儿筛查疑似3-甲基巴豆酰辅酶 A 羧化酶缺乏症的患儿进行基因突变分析，揭示其分子病因。方法 PCR 结合 Sanger 测序对患儿 MCCC1基因和MCCC2基因的全部外显子及其旁侧序列进行分析，检测其中可能存在的基因变异，应用 SIFT、PolyPhen-2在线软件预测突变对蛋白功能影响，并查询比对突变所在位置在不同物种间的保守性。采用 Human Splicing Finder 和 Swiss-PdbViewer 4.1.0软件分析基因变异导致疾病发生的可能机制。结果患儿 MCCC1基因检测到两个杂合突变，分别为 c.539G>T(p.G180V)和 c.704_711del(p.A235Vfs?4)，家系分析显示，前者遗传于父亲，后者遗传于母亲。这两个突变均可改变蛋白质的结构，从而对 MCC 蛋白功能造成影响。结论 MCCC1基因 c.539G>T(p.G180V)和 c.704_711del(p.A235Vfs?4)复合杂合突变可能是导致患儿 MCCD 的分子病因。
Objective To explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.Methods PCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes.SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species.Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.Results For the proband,a compound heterozygous mutation was discovered in the MCCC1 gene,namely c.539G>T (p.G180V)and c.704_71 1del (p.A235Vfs?4),which were inherited from his father and mother,respectively.The two mutations have disrupted the protein conformation,which in turn may impact the function of MCC protein.Conclusion The compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.
Objective To explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.Methods PCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes.SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species.Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.Results For the proband,a compound heterozygous mutation was discovered in the MCCC1 gene,namely c.539G>T (p.G180V)and c.704_71 1del (p.A235Vfs?4),which were inherited from his father and mother,respectively.The two mutations have disrupted the protein conformation,which in turn may impact the function of MCC protein.Conclusion The compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.