Clinical Characteristics and Gene Mutation Analysis of Methylmalonic Aciduria

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 31; no. 3; pp. 384 - 389
• Main Author: 易琴 吕娟娟 田凤艳 魏虹 宁琴 罗小平
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.06.2011
• Subjects: aciduria; adenosylcobalamin; Asian Continental Ancestry Group - genetics; Base Sequence; Cbl protein; Child, Preschool; chromosome 6; Cofactors; Complementation; DNA; DNA Mutational Analysis; Enzymes; Exons; Female; Fumarates - urine; Gas chromatography; genomics; Genotype; Hereditary diseases; Humans; Infant; Infant, Newborn; Male; Maleates - urine; Mass spectroscopy; Medicine; Medicine & Public Health; Metabolism, Inborn Errors - genetics; Methylmalonyl-CoA Mutase - deficiency; Methylmalonyl-CoA Mutase - genetics; Molecular Sequence Data; Mutation; Point mutation; Polymorphism, Genetic; Single-nucleotide polymorphism; 丙二酸; 临床特征; 单核苷酸多态性; 基因突变分析; 基因组DNA提取; 气相色谱/质谱; 甲基丙烯酸甲酯; 遗传疾病; methylmalonic aciduria; single nucleotide polymorphism; gene mutation; MUT gene
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-011-0386-3

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.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.