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

被引：27
作者：
Alders, Marielle [1 ]
Maas, Saskia M. [1 ,2 ]
Kadouch, Daniel J. M. [3 ]
van der Lip, Karin [1 ]
Bliek, Jet [1 ]
van der Horst, Chantal M. A. M. [4 ]
Mannens, Marcel M. A. M. [1 ]
机构：
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, NL-1105 AZ Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Plast & Reconstruct Surg, NL-1105 AZ Amsterdam, Netherlands
来源：
EUROPEAN JOURNAL OF MEDICAL GENETICS | 2014年 / 57卷 / 06期
关键词：
Beckwith-Wiedemann syndrome; Uniparental disomy (UPD); Mosaicism; BECKWITH-WIEDEMANN-SYNDROME; UNIPARENTAL DISOMY; TUMOR RISK; KCNQ1OT1; H19;
D O I：
10.1016/j.ejmg.2014.03.011
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
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. (C) 2014 Elsevier Masson SAS. All rights reserved.
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收藏
页码：293 / 297
页数：5
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