Frameshift Mutations at the C-terminus of HIST1H1E Result in a Specific DNA Hypomethylation Signature

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2020 Jan 9

PMID 31910894

Citations 30

Authors

Andrea Ciolfi

Erfan Aref-Eshghi

Simone Pizzi

Lucia Pedace

Evelina Miele

Jennifer Kerkhof

Elisabetta Flex

Simone Martinelli

Francesca Clementina Radio

Claudia A L Ruivenkamp

Gijs W E Santen

Emilia Bijlsma

Daniela Barge-Schaapveld

Katrin Ounap

Victoria Mok Siu

R Frank Kooy

Bruno Dallapiccola

Bekim Sadikovic

Marco Tartaglia

Affiliations

Soon will be listed here.

Abstract

Background: We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern.

Results: Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject.

Conclusions: We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis.

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