Naslov
Multiple methylation errors at imprinting control regions in patients with S-adenosylhomocysteine hydrolase (AHCY) deficiency

Autori
Antje Motzek, Jelena Knezevic, Mirjana Polović, Ulrich Zechner, Robert Belužić, Oliver Vugrek

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
25th German Society of Human Genetics

Mjesto i datum
Dresden, Njemačka, 2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
AHCY, AHCY deficiency, methylation

Sažetak
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a novel human disease, which was first discovered in Croatia in 2004. Main characteristics are psychomotor delay and severe myopathy (hypotonia, absent tendon reflexes and delayed myelination) from birth, associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome-wide DNA methylation. The prime function of AHCY is the efficient removal of S-adenosylhomocysteine (SAH), the by-product of transmethylation reactions. As SAH is one of the most potent methyltransferase inhibitors, its rapid removal is crucial to avoid product inhibition of methyltransferases. Thus, AHCY plays a critical role in regulation of biological methylation processes. We set out to more specifically characterize DNA methylation changes in blood DNA samples of five AHCY-deficient patients as well as HepG2 and HEK293 cell lines after shRNA-mediated knockdown of the AHCY gene by determining the quantitative DNA methylation patterns of different imprinting control regions (ICRs). Two of the analyzed patients showed aberrant hypermethylation at all up to now analyzed ICRs (MEST, NESPAS, SNRPN and PEG3) whereas the remaining three patients displayed normal differential methylation patterns. The knockdown cell lines also exhibited methylation changes to different degrees at the ICRs. Microarray-based experiments to analyze the complete DNA methylome of AHCY-deficient patients in comparison to normal individuals are planned. Our preliminary data indicate that AHCY deficiency may represent a good model disease for studying the biological consequences of multiple methylation errors in epigenetic research. Thus, findings from this study may make an important contribution to develop standard and high-throughput tools for the diagnosis of AHCY deficiency and other diseases associated with aberrant epigenetic modifications.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA