The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

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
Show all

Summary, in English

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.

Department/s

  • Matrix Biology

Publishing year

2016-02-18

Language

English

Pages

147-155

Publication/Series

Molecular Medicine

Volume

22

Document type

Journal article

Publisher

The Feinstein Institute for Medical Research

Topic

  • Medical Genetics

Status

Published

Research group

  • Matrix Biology

ISBN/ISSN/Other

  • ISSN: 1528-3658