Identification of two novel mutations of MUT gene in a Chinese family affected with isolated methylmalonic acidemia.
- VernacularTitle:一个单纯性甲基丙二酸血症家系中MUT基因两个新突变的鉴定
- Author:
Bobo XIE
1
;
Jingsi LUO
;
Xin FAN
;
Rongyu CHEN
;
Jin WANG
;
Shujie ZHANG
;
Wang LI
;
Shaoke CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Amino Acid Metabolism, Inborn Errors; enzymology; genetics; Amino Acid Sequence; Animals; Asian Continental Ancestry Group; genetics; Base Sequence; China; Female; Humans; Infant; Male; Methylmalonyl-CoA Mutase; genetics; Molecular Sequence Data; Mutation; Mutation, Missense; Pedigree; Point Mutation; Sequence Alignment
- From: Chinese Journal of Medical Genetics 2016;33(2):135-139
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the molecular etiology for a Chinese family affected with isolated methylmalonic acidemia (MMA).
METHODSPotential mutations of MUT, MMAA and MMAB genes in the proband were screened by PCR and Sanger sequencing. The pathogenicity of identified mutations was analyzed using Polyphen2, SIFT, HSF, DNAMAN 6.0 and Swiss-PdbViewer4.1.0 software.
RESULTSTwo novel mutations of the MUT gene, including c.581C>T (p.P194L) and c.1219A>T (p.N407Y), were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that both mutations were damaging. The affected codons P194 and N407, both located in the (beta, alpha) 8 barrel domain and to which the substrate methylmalonyl-CoA is bound, are highly conserved across various species. Both mutations can disrupt the space conformation of its protein product, affecting the function of the MCM protein.
CONCLUSIONThe novel mutations of MUT gene probably underlie the isolated MMA in this family.
