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Published on: June 13, 2019
Epigenotype, phenotype, and tumors in patients with isolated hemihyperplasia
Jet Bliek1, Saskia Maas, Mariel Alders
1Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands. j.bliek@amc.uva.nl
Objective:
To investigate whether epigenotyping of patients with isolated hemihyperplasia (IH) can, analogous to genetic screening of patients with Beckwith-Wiedemann syndrome, be used for the prediction of tumor risk and tumor type of individual patients.
Study Design:
Methylation analysis of H19 and KCNQ1OT1 of 73 patients. Questionnaires were sent to referring clinicians.
Results:
In 75% of the clinically confirmed patients with IH no epigenetic defect was detected. Paternal uniparental disomy was found in 15%, demethylation of KCNQ1OT1 in only 6%, and hypermethylation of H19 in 3% of isolated hemihyperplasia cases. Ten percent of the patients with IH had development of a childhood tumor associated with paternal uniparental disomy (2/8) or no methylation defect (2/30). No genetic defect was detected in 10 of 14 additional patients with cancer with IH. In these latter patients, a methylation defect of H19 was seen 3 times and a paternal uniparental disomy once. The female-to-male ratio was 6:1.
Conclusions:
Aberrant methylation of the 11p15 region is not common in patients with IH and can at present not be used for tumor risk determination.
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