title: [Analysis of the MUT gene mutations in patients with methylmalonic acidemia].
abstract: OBJECTIVE
  To investigate the MUT gene mutations in patients with methylmalonic acidemia (MMA), and analyze the genotype-phenotype correlation in patients with methylmalonyl-CoA mutase deficiency.
  
  
  METHODS
  The diagnosis of the disease mainly depends on the measurement of C3 (acylcarnitine), C3/C0 (free carnitine) and C3/C2 (acetylcarnitine) in the blood by tandem mass spectrometry, the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry, the determination of total homocysteine in the serum, and the loading test of vitamin B(12). The entire coding region of the MUT gene was screened by PCR combined with direct DNA sequencing in 21 isolated MMA patients. Novel mutations were identified by restriction fragment length polymorphism (RFLP) and sequence analysis in 100 controls.
  
  
  RESULTS
  Seventeen MUT gene mutations were detected in 14 of the 21 patients, among them 8 mutations were novel, and R108H, D244LfsX39 and G544X were more frequent, with the frequencies of 9.5%, 7.1% and 9.5%, respectively. Most mutations were missense mutations (64.7%), and majority of them were in exons 2 and 3 (55.6%). Ten out of the 14 patients with MUT gene mutations had early-onset disease, while one case had late-onset disease, and the remaining 3 cases were detected by newborn screening. In addition, 11 of these 14 patients did not respond to vitamin B(12).
  
  
  CONCLUSIONS
  This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB(12)- non-responsive.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Lianshu
authors.initials: L
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Qiu
authors.forename: Yafen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D001483:Base Sequence; D002681:China; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008764:Methylmalonic Acid / Q000378:metabolism; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase