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 biallelic MAT1A mutations have been identified, respectively. Although most patients have benign clinical outcomes, some with the AR form have neur...
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doaj-e74cf6df38bb47809edb4041f0f508942020-11-24T21:45:00ZengBMCMolecular Medicine1076-15511528-36582016-02-0122114715510.2119/molmed.2015.00254Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular StudiesYoo-Mi Kim0Ja Hye Kim1Jin-Ho Choi2Gu-Hwan Kim3Jae-Min Kim4Minji Kang5In-Hee Choi6Chong Kun Cheon7Young Bae Sohn8Marco Maccarana9Han-Wook Yoo10Beom Hee Lee11Department of Pediatrics, College of Medicine, Pusan National University Children’s HospitalDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineDepartment of Pediatrics, College of Medicine, Pusan National University Children’s HospitalDepartment of Medical Genetics, Ajou University Hospital, Ajou University School of MedicineDepartment of Experimental Medical Science, BMC, Lund UniversityMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineMedical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineAbstract Methionine adenosyltransferase (MAT) I/III deficiency can be Inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or biallelic MAT1A mutations 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 AD MAT1A mutation, 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.http://link.springer.com/article/10.2119/molmed.2015.00254 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoo-Mi Kim Ja Hye Kim Jin-Ho Choi Gu-Hwan Kim Jae-Min Kim Minji Kang In-Hee Choi Chong Kun Cheon Young Bae Sohn Marco Maccarana Han-Wook Yoo Beom Hee Lee |
spellingShingle |
Yoo-Mi Kim Ja Hye Kim Jin-Ho Choi Gu-Hwan Kim Jae-Min Kim Minji Kang In-Hee Choi Chong Kun Cheon Young Bae Sohn Marco Maccarana Han-Wook Yoo Beom Hee Lee Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies Molecular Medicine |
author_facet |
Yoo-Mi Kim Ja Hye Kim Jin-Ho Choi Gu-Hwan Kim Jae-Min Kim Minji Kang In-Hee Choi Chong Kun Cheon Young Bae Sohn Marco Maccarana Han-Wook Yoo Beom Hee Lee |
author_sort |
Yoo-Mi Kim |
title |
Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies |
title_short |
Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies |
title_full |
Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies |
title_fullStr |
Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies |
title_full_unstemmed |
Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies |
title_sort |
determination of autosomal dominant or recessive methionine adenosyltransferase i/iii deficiencies based on clinical and molecular studies |
publisher |
BMC |
series |
Molecular Medicine |
issn |
1076-1551 1528-3658 |
publishDate |
2016-02-01 |
description |
Abstract Methionine adenosyltransferase (MAT) I/III deficiency can be Inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or biallelic MAT1A mutations 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 AD MAT1A mutation, 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. |
url |
http://link.springer.com/article/10.2119/molmed.2015.00254 |
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