Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood

Mariëlle Alders; Saskia M Maas; Daniël J M Kadouch; Karin van der Lip; Jet Bliek; Chantal M A M van der Horst; Marcel M A M Mannens

doi:10.1016/j.ejmg.2014.03.011

Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood

Eur J Med Genet. 2014 May-Jun;57(6):293-7. doi: 10.1016/j.ejmg.2014.03.011. Epub 2014 Apr 2.

Authors

Mariëlle Alders¹, Saskia M Maas², Daniël J M Kadouch³, Karin van der Lip⁴, Jet Bliek⁴, Chantal M A M van der Horst⁵, Marcel M A M Mannens⁴

Affiliations

¹ Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: m.alders@amc.uva.nl.
² Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
³ Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
⁴ Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
⁵ Department of Plastic and Reconstructive Surgery, Academic Medical Center, Amsterdam, The Netherlands.

PMID: 24704790
DOI: 10.1016/j.ejmg.2014.03.011

Abstract

The Beckwith-Wiedemann syndrome is caused by disturbed imprinting of genes at 11p15.5. Routine diagnostic testing for Beckwith-Wiedemann syndrome (BWS) includes methylation analysis of the imprinting centers ICR1 and ICR2 in DNA extracted from lymphocytes. In approximately 15% of BWS patients the diagnosis cannot be molecularly confirmed. In this study we determined the methylation status in resected tongue tissue of 11 BWS patients and compared this to the genetic defects found by routine diagnostic screening of blood lymphocytes. In all three patients with normal methylation levels in blood, aberrant methylation patterns were found in tongue tissue. In two patients a UPD was detected and the third case had hypermethylation of ICR1. This result shows that tissue specific mosaic (epi)genetic changes, not present in blood, is the underlying defect in at least a subset of BWS patients without a molecular diagnosis after standard genetic testing.

Keywords: Beckwith–Wiedemann syndrome; Mosaicism; Uniparental disomy (UPD).

MeSH terms

Beckwith-Wiedemann Syndrome / blood
Beckwith-Wiedemann Syndrome / genetics*
DNA Methylation*
Female
Genomic Imprinting*
Humans
Infant
Male
Tongue / metabolism*
Uniparental Disomy