ProjectEpiProspects: Evaluating prospects of epigenome profiling in unsolved syndromal cases

Basic data

EpiProspects: Evaluating prospects of epigenome profiling in unsolved syndromal cases
01/08/2021 to 31/07/2023
Abstract / short description:
While whole exome and genome sequencing have been proven to be a powerful tool in routine diagnostics to establish new disease genes and molecular diagnoses, they can only solve about 40% of all cases. Sequencing other molecular layers - foremost the epigenome - which is not part of routine diagnostics yet, might help to fill this gap. In particular, defects in DNA methylation have long been known to be involved in a certain group of constitutional syndromes such as imprinting disorders. Recently, other cases have been shown to result from DNA methylation defects at a single locus (epi-variants), or can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures).
Profiling the DNA methylome complemented by a transcriptome and integrating these rich sequencing data, hence, promises to yield a higher rate of solved cases and a more complete picture of the etiology and underlying disease mechanisms.
Here, we propose to use a unique collection of 35 syndromal patient samples for which trio genome sequencing did not yield causal variants as well as 15 patients with known mutations in epigenetic regulators as positive controls. Complemented by a transcriptome, we aim to profile these index patients’ as well as healthy siblings’ and parents’ DNA methylome in keratinocytes. We will then individually analyze and integrate these data, in order to identify underlying disease causes and understand which layers need to be profiled for a comprehensive diagnosis. Ultimately, our project will help to evaluate the prospects of DNA methylome profiling to solve heritable diseases and develop standard operation procedures for routine diagnostics.
rare disease
Seltene Erkrankung

Involved staff


Faculty of Medicine
University of Tübingen

Contact persons

Faculty of Medicine
University of Tübingen

Local organizational units

Institute of Medical Genetics and Applied Genomics
Department of Diagnostic Laboratory Medicine
Hospitals and clinical institutes, Faculty of Medicine


Bonn, Nordrhein-Westfalen, Germany

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