title: Clinical features and MUT gene mutation spectrum in Chinese patients with isolated methylmalonic acidemia: identification of ten novel allelic variants.
abstract: BACKGROUND
  This study aims to study MUT gene mutation spectrum in Chinese patients with isolated methylmalonic academia (MMA) and their clinical features for the potential genotype-phenotype correlation.
  
  
  METHODS
  Forty-three patients were diagnosed with isolated MMA by elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and urine methylmalonate without hyperhomocysteinemia. The MUT gene was amplified by polymerase chain reaction and directly sequenced. Those patients with at least one variant allele were included. The novel missense mutations were assessed by bioinformatic analysis and screened against alleles sequenced from 50 control participants.
  
  
  RESULTS
  Among the 43 patients, 38 had typical clinical presentations, and the majority (30/38) experienced earlyonset MMA. Eight patients died and seven were lost to follow-up. Twenty patients had poor outcomes and eight showed normal development. The 43 identified MUT gene mutations had at least one variant allele, whereas 35 had two mutant alleles. Of the 33 mutations reported before, eight recurrent mutations were identified in 32 patients, and c.729_730insTT (p.D244Lfs*39) was the most common (12/78) in the mutant alleles. Of the 10 novel mutations, six were missense mutations and four were premature termination codon mutations. The six novel missense mutations seemed to be pathogenic.
  
  
  CONCLUSIONS
  A total of 10 novel MUT mutations were detected in the Chinese population. c.729_730insTT (p.D244Lfs*39) was the most frequent mutation. A genotype-phenotype correlation could not be found, but the genotypic characterization indicated the need of genetic counseling for MMA patients and early prenatal diagnoses for high-risk families.
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lian-Shu
authors.initials: LS
authors.lastname: Han
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Qiu
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: , Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhu-Wen
authors.initials: ZW
authors.lastname: Gong
authors.affiliation: , Shanghai, China. gu_xuefan@163.com.|Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China. gu_xuefan@163.com.
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Gu
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors; D044466:Asian People / Q000235:genetics; D002681:China; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D008765:Methylmalonyl-CoA Mutase
keywords: MUT gene; methylmalonic acidemia; missense mutation