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Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies.

Kim, Yoo-Mi; Kim, Ja Hye; Choi, Jin-Ho; Kim, Gu-Hwan; Kim, Jae-Min; Kang, Minji; Choi, In-Hee; Cheon, Chong Kun; Sohn, Young Bae and Maccarana, Marco LU , et al. (2016) In Molecular Medicine 22. p.147-155
Abstract
Methionine adenosyltransferase (MAT) I/III deficiency can be inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or bi-allelic 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 vs. 733.2 μmol/L, P < 0.05) and homocysteine levels (12.3 μmol/L vs. 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,... (More)
Methionine adenosyltransferase (MAT) I/III deficiency can be inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or bi-allelic 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 vs. 733.2 μmol/L, P < 0.05) and homocysteine levels (12.3 μmol/L vs. 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 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. (Less)
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Molecular Medicine
volume
22
pages
147 - 155
publisher
The Feinstein Institute for Medical Research
external identifiers
  • PMID:26933843
  • Scopus:84987667604
  • WOS:000381523400001
ISSN
1528-3658
DOI
10.2119/molmed.2015.00254
language
English
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yes
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a2bd28a6-1f44-468e-80ac-b11f65519ef2 (old id 8856511)
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http://www.ncbi.nlm.nih.gov/pubmed/26933843?dopt=Abstract
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2016-03-16 10:48:06
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2017-01-01 07:44:11
@article{a2bd28a6-1f44-468e-80ac-b11f65519ef2,
  abstract     = {Methionine adenosyltransferase (MAT) I/III deficiency can be inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or bi-allelic 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 vs. 733.2 μmol/L, P &lt; 0.05) and homocysteine levels (12.3 μmol/L vs. 18.6 μmol/L, P &lt; 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 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.},
  author       = {Kim, Yoo-Mi and Kim, Ja Hye and Choi, Jin-Ho and Kim, Gu-Hwan and Kim, Jae-Min and Kang, Minji and Choi, In-Hee and Cheon, Chong Kun and Sohn, Young Bae and Maccarana, Marco and Yoo, Han-Wook and Lee, Beom Hee},
  issn         = {1528-3658},
  language     = {eng},
  month        = {02},
  pages        = {147--155},
  publisher    = {The Feinstein Institute for Medical Research},
  series       = {Molecular Medicine},
  title        = {Determination of Autosomal Dominant or Recessive Methionine Adenosyltransferase I/III Deficiencies Based on Clinical and Molecular Studies.},
  url          = {http://dx.doi.org/10.2119/molmed.2015.00254},
  volume       = {22},
  year         = {2016},
}