Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood |
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| Affiliation: | 1. Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan;2. Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan;3. Department of Maternal–Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan;4. Education Center, Asahikawa Medical University, Asahikawa, Japan;5. Department of Pediatrics, Maternal, Perinatal, and Child Medical Center, Tenshi Hospital, Sapporo, Japan;6. Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan;7. Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan;8. Division of Medical Genetics, Saitama Children’s Medical Center, Saitama, Japan;9. Department of Pediatrics, Nippon Medical School, Tokyo, Japan;10. Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan;11. Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan;12. Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan;13. Nishikyushu University, Saga, Japan;1. Bipolar Disorder Program, Institute of Neurosciences, Favaloro University, Buenos Aires, Argentina;2. Institute of Cognitive Neurology (INECO), Buenos Aires, Argentina |
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| 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. |
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| Keywords: | Beckwith–Wiedemann syndrome Uniparental disomy (UPD) Mosaicism |
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