Publication: Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
Issued Date
2012-08-01
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ISSN
10967206
10967192
10967192
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2-s2.0-84864345932
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Genetics and Metabolism. Vol.106, No.4 (2012), 424-429
Suggested Citation
Nithiwat Vatanavicharn, Voraratt Champattanachai, Somporn Liammongkolkul, Phannee Sawangareetrakul, Siriporn Keeratichamroen, James R. Ketudat Cairns, Chantragan Srisomsap, Achara Sathienkijkanchai, Vorasuk Shotelersuk, Mahattana Kamolsilp, Duangrurdee Wattanasirichaigoon, Jisnuson Svasti, Pornswan Wasant Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia. Molecular Genetics and Metabolism. Vol.106, No.4 (2012), 424-429. doi:10.1016/j.ymgme.2012.05.012 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/13657
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Title
Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
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Abstract
Isolated methylmalonic acidemia (MMA) is a genetically heterogeneous organic acid disorder caused by either deficiency of the enzyme methylmalonyl-CoA mutase (MCM), or a defect in the biosynthesis of its cofactor, adenosyl-cobalamin (AdoCbl). Herein, we report and review the genotypes and phenotypes of 14 Thai patients with isolated MMA. Between 1997 and 2011, we identified 6 . mut patients, 2 . cblA patients, and 6 . cblB patients. The . mut and . cblB patients had relatively severe phenotypes compared to relatively mild phenotypes of the . cblA patients. The . MUT and . MMAB genotypes were also correlated to the severity of the phenotypes. Three mutations in the . MUT gene: c.788G > T (p.G263V), c.809_812dupGGGC (p.D272Gfs*2), and c.1426C > T (p.Q476*); one mutation in the . MMAA gene: c.292A > G (p.R98G); and three mutations in the . MMAB gene: c.682delG (p.A228Pfs*2), c.435delC (p.F145Lfs*69), and c.585-1G > A, have not been previously reported. RT-PCR analysis of a common intron 6 polymorphism (c.520-159C > T) of the . MMAB gene revealed that it correlates to deep intronic exonization leading to premature termination of the open reading frame. This could decrease the ATP:cobalamin adenosyltransferase (ATR) activity resulting in abnormal phenotypes if found in a compound heterozygous state with a null mutation. We confirm the genotype-phenotype correlation of isolated MMA in the study population, and identified a new molecular basis of the . cblB disorder. © 2012 Elsevier Inc.