Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified

A Atfi

A Brunet

A Eijkelenboom

A Madej-Pilarczyk

A Maierhofer

BC Capell

C Bes

C Kayser

C Lok

CI Weidner

D Grafodatskaya

DN Edwards

EK Yeong

EL Greer

EY Chen

F Coppede

F Hoogen van den

G Valentini

H Heyn

H Imura

HH Adams

HH Cheung

J Dumas

J Peltier

K Murata

KA Cho

M Goto

M Muftuoglu

M Takemoto

ME Hettema

MF Giacomin

MG Bacalini

MJ Hernandez-Corbacho

ML Rossi

MV Kuleshov

N Altorok

N Hay

P Du

R Jennemann

RM Silver

S Zhang

SV Jovanovic

T Barrett

T Taniguchi

TR Luckhardt

UF Haustein

WT Brown

X Zhu

English

Background: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified.Results: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome.Conclusions: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status

Guastafierro, T.

Bacalini, M. G.

Marcoccia, A.

Gentilini, D.

Pisoni, S.

Di Blasio, A. M.

Corsi, A.

Franceschi, C.

Raimondo, D.

Spanò, A.

Garagnani, P.

Bondanini, F.

ZENODO

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Guastafierro, T

Bacalini, MG

Marcoccia, A

Gentilini, D

Pisoni, S

Di Blasio, A M

Corsi, A

Franceschi, C

Raimondo, D

Spanò, A

Garagnani, P

Bondanini, F

Archivio istituzionale della ricerca - Alma Mater Studiorum Università di Bologna

NEUROSURGERY ENTHUSIASTIC WOMEN SOCIETY

Background
Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified.
Results
To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome.
Conclusions
DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status

Spanò, A.

Archivio della ricerca- Università di Roma La Sapienza

T. Guastafierro

M. G. Bacalini

A. Marcoccia

D. Gentilini

S. Pisoni

A. M. Di Blasio

A. Corsi

C. Franceschi

D. Raimondo

A. Spanò

P. Garagnani

F. Bondanini

Crossref

Clinical Epigenetics

Di, Blasio AM

Spano, A

Swepub

Abstract Background Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. Results To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. Conclusions DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status

Directory of Open Access Journals

https://iris.uniroma1.it/bitstream/11573/1004141/1/Guastafierro_Genome-wide_2017.pdf

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Abstract

Similar works

Full text

Available Versions