Genome-wide paternal uniparental disomy mosaicism in a woman with Beckwith-Wiedemann syndrome and ovarian steroid cell tumour

被引:34
作者
Gogiel, Magdalena [1 ]
Begemann, Matthias [1 ]
Spengler, Sabrina [1 ]
Soellner, Lukas [1 ]
Goeretzlehner, Ulf [2 ]
Eggermann, Thomas [1 ]
Strobl-Wildemann, Gertrud
机构
[1] Rhein Westfal TH Aachen, Inst Human Genet, D-52074 Aachen, Germany
[2] Gynaecol Hosp, Dept Gynaecol, Ehingen, Germany
关键词
Beckwith-Wiedemann syndrome; cancer; genomic imprinting; PLACENTAL MESENCHYMAL DYSPLASIA; ANDROGENETIC/BIPARENTAL MOSAICISM; IMPRINTED LOCI; METHYLATION; EXPRESSION; GENE; H19;
D O I
10.1038/ejhg.2012.259
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Uniparental disomy (UPD) of single chromosomes is a well-known molecular aberration in a group of congenital diseases commonly known as imprinting disorders (IDs). Whereas maternal and/or paternal UPD of chromosomes 6, 7, 11, 14 and 15 are associated with specific IDs (Transient neonatal diabetes mellitus, Silver-Russell syndrome, Beckwith-Wiedemann syndrome (BWS), upd(14)-syndromes, Prader-Willi syndrome, Angelman Syndrome), the other autosomes are not. UPD of the whole genome is not consistent with life, in case of non-mosaic genome-wide paternal UPD (patUPD) it leads to hydatidiform mole. In contrast, mosaic genome-wide patUPD might be compatible with life. Here we present a 19-year-old woman with BWS features and initially diagnosed to be carrier of a mosaic patUPD of chromosome 11p15. However, the patient presented further clinical findings not typically associated with BWS, including nesidioblastosis, fibroadenoma, hamartoma of the liver, hypoglycaemia and ovarian steroid cell tumour. Additional molecular investigations revealed a mosaic genome-wide patUPD. So far, only nine cases with mosaic genome-wide patUPD and similar clinical findings have been reported, but these patients were nearly almost diagnosed in early childhood. Summarising the data from the literature and those from our patient, it can be concluded that the mosaic genome-wide patUPD (also known as androgenic/biparental mosaicism) might explain unusual BWS phenotypes. Thus, these findings emphasise the need for multilocus testing in IDs to efficiently detect cases with disturbances affecting more than one chromosome.
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收藏
页码:788 / 791
页数:4
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