title: Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies.
abstract: Methionine adenosyltransferase (MAT) I/III deficiency can be inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or biallelicMAT1Amutations have been identified, respectively. Although most patients have benign clinical outcomes, some with the AR form have neurological deficits. Here we describe 16 Korean patients with MAT I/III deficiency from 15 unrelated families identified by newborn screening. Ten probands had the AD MAT I/III deficiency, while six had AR MAT I/III deficiency. Plasma methionine (145.7 μmol/L versus 733.2 μmol/L,P< 0.05) and homocysteine levels (12.3 μmol/L versus 18.6 μmol/L,P< 0.05) were lower in the AD type than in AR type. In addition to the only reported ADMAT1Amutation, p.Arg264His, we identified two novel AD mutations, p.Arg249Gln and p.Gly280Arg. In the AR type, four previously reported and two novel mutations, p.Arg163Trp and p.Tyr335*, were identified. No exonic deletions were found by quantitative genomic polymerase chain reaction (PCR). Three-dimensional structural prediction programs indicated that the AD-type mutations were located on the dimer interface or in the substrate binding site, hindering MAT I/III dimerization or substrate binding, respectively, whereas the AR mutations were distant from the interface or substrate binding site. These results indicate that the AD or AR MAT I/III deficiency is correlated with clinical findings, substrate levels and structural features of the mutant proteins, which is important for the neurological management and genetic counseling of the patients.
authors.affiliation: Department of Pediatrics, College of Medicine, Pusan National University Children's Hospital, Yangsan, Korea.
authors.forename: Yoo-Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ja Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Choi
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kim
authors.initials: K
authors.lastname: Gu-Hwan
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Minji
authors.initials: M
authors.lastname: Kang
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, College of Medicine, Pusan National University Children's Hospital, Yangsan, Korea.
authors.forename: Chong Kun
authors.initials: CK
authors.lastname: Cheon
authors.affiliation: Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Sohn
authors.affiliation: Department of Experimental Medical Science, BMC, Lund University, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee