title: [Identification of two novel mutations of MUT gene in a Chinese family affected with isolated methylmalonic acidemia].
abstract: OBJECTIVE
  To explore the molecular etiology for a Chinese family affected with isolated methylmalonic acidemia (MMA).
  
  
  METHODS
  Potential 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.
  
  
  RESULTS
  Two 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.
  
  
  CONCLUSIONS
  The novel mutations of MUT gene probably underlie the isolated MMA in this family.
authors.affiliation: Department of Genetic Metabolism, Obstetrics and Gynecology Hospital, Maternal and Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530000, China. chenshaoke123@163.com.
authors.forename: Bobo
authors.initials: B
authors.lastname: Xie
authors.forename: Jingsi
authors.initials: J
authors.lastname: Luo
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.forename: Rongyu
authors.initials: R
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Shujie
authors.initials: S
authors.lastname: Zhang
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D016415:Sequence Alignment
chemical_list: D008765:Methylmalonyl-CoA Mutase