title: Analysis of Novel Mutations and Methylmalonyl-CoA Mutase Levels in Thai Patients with Isolated Methylmalonic Acidemia.
abstract: Isolated methylmalonic acidemia (MMA) is an autosomal recessive, inherited disorder that results from either a mut defect of the methylmalonyl-CoA mutase apoenzyme (MCM, the product of the MUT gene) or a cbl defect in the synthesis of its cofactor, adenosylcobalamin (AdoCbl). In this study, biochemical and mutational analyses of three patients clinically diagnosed with MMA were performed. No MCM activity was detected in leukocyte extracts of two patients, while high MCM activity was found in the other, suggesting mut (0) and cbl defects, respectively. A novel (c.IVS6 -3 to -8delCTTTTT, p.K444_L445insFC*) and two known mutations in the MUT gene and one novel (c.227_36delGACCCAAAGA, p.R76Mfs*14) mutation in the MMAB gene were identified. In addition, MCM immunoblot analysis of leukocyte extract samples of these three patients and eight patients previously reported by our group, as well as their parents, showed a good correlation between the MCM protein and activity levels. Patients with mut (0) defective subtypes lacked MCM activity and had no MCM band, while patients carrying the cbl defects had high MCM activity levels and an intense MCM band at about 83 kDa, in comparison to those in their parents. These data expand the mutation spectrum of MMA deficiency. In addition, the examination of MCM protein level may be used as an alternative technique to determine the mut (0) and cbl defective subgroups.
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand.
authors.forename: Phannee
authors.initials: P
authors.lastname: Sawangareetrakul
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand.|School of Biochemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
authors.forename: James R
authors.initials: JR
authors.lastname: Ketudat Cairns
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Nithiwat
authors.initials: N
authors.lastname: Vatanavicharn
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Somporn
authors.initials: S
authors.lastname: Liammongkolkul
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Pornswan
authors.initials: P
authors.lastname: Wasant
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand.|Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, 10210, Thailand.
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand. voraratt@cri.or.th.|Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, 10210, Thailand. voraratt@cri.or.th.
authors.forename: Voraratt
authors.initials: V
authors.lastname: Champattanachai
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation
chemical_list: D019883:Alkyl and Aryl Transferases; C019920:cob(I)alamin adenosyltransferase; D008765:Methylmalonyl-CoA Mutase
keywords: Adenosylcobalamin; Methylmalonic acidemia; Methylmalonyl-CoA mutase; Mutation