Motzek, Antje and Knežević, Jelena and Switzeny, Olivier J. and Cooper, Alexis and Barić, Ivo and Belužić, Robert and Strauss, Kevin A. and Puffenberger, Erik G. and Mudd, S. Harvey and Vugrek, Oliver and Zechner, Ulrich (2016) Abnormal hypermethylation at imprinting control regions in patients with S-adenosylhomocysteine hydrolase (AHCY) deficiency. PLoS ONE, 11 (3). e0151261. ISSN 1932-6203
![[img]](http://medlib.mef.hr/style/images/fileicons/application_pdf.png) |
PDF
- Published Version
Download (1MB) |
Abstract
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors. In this study, we set out to more specifically characterize DNA methylation changes in blood samples from patients with AHCY deficiency. Global DNA methylation was increased in two of three analysed patients. In addition, we analysed the DNA methylation levels at differentially methylated regions (DMRs) of six imprinted genes (MEST, SNRPN, LIT1, H19, GTL2 and PEG3) as well as Alu and LINE1 repetitive elements in seven patients. Three patients showed a hypermethylation in up to five imprinted gene DMRs. Abnormal methylation in Alu and LINE1 repetitive elements was not observed. We conclude that DNA hypermethylation seems to be a frequent but not a constant feature associated with AHCY deficiency that affects different genomic regions to different degrees. Thus AHCY deficiency may represent an ideal model disease for studying the molecular origins and biological consequences of DNA hypermethylation due to impaired cellular methylation status.
| Item Type: | Article | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Additional Information: | © 2016 Motzek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||||||||||||||||||||||||
| MeSH: | Alu Elements ; Amino Acid Metabolism, Inborn Errors/blood ; Amino Acid Metabolism, Inborn Errors/genetics ; Creatine/blood ; DNA Methylation ; Female ; Genomic Imprinting ; Glycine N-Methyltransferase/blood ; Glycine N-Methyltransferase/deficiency ; Glycine N-Methyltransferase/genetics ; Humans ; Infant ; Infant, Newborn ; Long Interspersed Nucleotide Elements ; Male | ||||||||||||||||||||||||
| Departments: | Katedra za pedijatriju | ||||||||||||||||||||||||
| Depositing User: | Martina Žužak | ||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||
| Creators: |
|
||||||||||||||||||||||||
| Date: | 14 March 2016 | ||||||||||||||||||||||||
| Date Deposited: | 04 Oct 2017 10:04 | ||||||||||||||||||||||||
| Last Modified: | 12 Aug 2020 07:01 | ||||||||||||||||||||||||
| Subjects: | UNSPECIFIED | ||||||||||||||||||||||||
| Related URLs: | |||||||||||||||||||||||||
| URI: | http://medlib.mef.hr/id/eprint/2694 |
Actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
