title: Clinical characteristics and gene mutation analysis of methylmalonic aciduria.
abstract: Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM, mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups). The defects in the mut complementation group accounts for the largest number of patients with isolated MMA. At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now. This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients. Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS), and from some of their parents as well. Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations. In this group, six novel mutations in the MUT gene, c.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A (p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.
authors.affiliation: Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430030, China. xpluo@tjh.tjmu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005650:Fumarates / Q000652:urine*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008298:Maleates / Q000652:urine*; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency* / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D005650:Fumarates; D008298:Maleates; C073341:citraconic acid; D008765:Methylmalonyl-CoA Mutase