Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood.
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.
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: m.alders@amc.uva.nl.
Mariëlle
M
Alders
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
Saskia M
SM
Maas
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
Daniël J M
DJ
Kadouch
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Karin
K
van der Lip
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Jet
J
Bliek
Department of Plastic and Reconstructive Surgery, Academic Medical Center, Amsterdam, The Netherlands.
Chantal M A M
CM
van der Horst
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Marcel M A M
MM
Mannens
D001506:Beckwith-Wiedemann Syndrome / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D008297:Male; D014059:Tongue / Q000378:metabolism*; D024182:Uniparental Disomy
Beckwith–Wiedemann syndrome; Mosaicism; Uniparental disomy (UPD)