Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia

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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Other Authors: Mahidol University
Format: Article
Published: 2018
Subjects:
Online Access:https://repository.li.mahidol.ac.th/handle/123456789/13657
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Mahidol University
id th-mahidol.13657
record_format dspace
spelling th-mahidol.136572018-06-11T12:07:46Z Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia 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 Mahidol University Chulabhorn Research Institute Suranaree University of Technology Chulalongkorn University King Chulalongkorn Memorial Hospital, Faculty of Medicine Chulalongkorn University Phramongkutklao College of Medicine Biochemistry, Genetics and Molecular Biology Medicine 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. 2018-06-11T04:35:00Z 2018-06-11T04:35:00Z 2012-08-01 Article Molecular Genetics and Metabolism. Vol.106, No.4 (2012), 424-429 10.1016/j.ymgme.2012.05.012 10967206 10967192 2-s2.0-84864345932 https://repository.li.mahidol.ac.th/handle/123456789/13657 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84864345932&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
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
description 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.
author2 Mahidol University
author_facet Mahidol University
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
format Article
author 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
author_sort Nithiwat Vatanavicharn
title Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
title_short Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
title_full Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
title_fullStr Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
title_full_unstemmed Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia
title_sort clinical and molecular findings in thai patients with isolated methylmalonic acidemia
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/13657
_version_ 1763497705871507456