Beygo, Jasmin, Elbracht, Miriam, de Groot, Karel ORCID: 0000-0003-4554-9796, Begemann, Matthias ORCID: 0000-0002-4659-8437, Kanber, Deniz, Platzer, Konrad ORCID: 0000-0001-6127-6308, Gillessen-Kaesbach, Gabriele, Vierzig, Anne, Green, Andrew ORCID: 0000-0002-1077-7417, Heller, Raoul, Buiting, Karin and Eggermann, Thomas (2015). Novel deletions affecting the MEG3-DMR provide further evidence for a hierarchical regulation of imprinting in 14q32. Eur. J. Hum. Genet., 23 (2). S. 180 - 189. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5438

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Abstract

The imprinted region on chromosome 14q32 harbors several maternally or paternally expressed genes as well as two DMRs (differentially methylated regions), the IG-DMR and the MEG3-DMR, which both act as imprinting control centers. Genetic aberrations affecting the imprinted gene cluster in 14q32 result in distinct phenotypes, known as maternal or paternal uniparental disomy 14 phenotypes (upd(14) mat, upd(14) pat). In both syndromes, three types of molecular alterations have been reported: uniparental disomy 14, deletions and epimutations. In contrast to uniparental disomy and epimutations, deletions affecting regulatory elements in 14q32 are associated with a high-recurrence risk. Based on two single deletion cases a functional hierarchy of the IG-DMR as a regulator for the methylation of the MEG3-DMR has been proposed. We have identified two novel deletions of maternal origin spanning the MEG3-DMR, but not the IG-DMR in patients with upd(14) pat syndrome, one de novo deletion of 165 kb and another deletion of 5.8 kb in two siblings. The 5.8 kb deletion was inherited from the phenotypically normal mother, who carries the deletion in a mosaic state on her paternal chromosome 14. The methylation at both DMRs was investigated by quantitative next generation bisulfite sequencing and revealed normal methylation patterns at the IG-DMR in all patients with the exception of certain CpG dinucleotides. Thus, we could confirm that deletions of the MEG3-DMR does not generally influence the methylation pattern of the IG-DMR, which strengthens the hypothesis of a hierarchical structure and distinct functional properties of the two DMRs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Beygo, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elbracht, MiriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Groot, KarelUNSPECIFIEDorcid.org/0000-0003-4554-9796UNSPECIFIED
Begemann, MatthiasUNSPECIFIEDorcid.org/0000-0002-4659-8437UNSPECIFIED
Kanber, DenizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platzer, KonradUNSPECIFIEDorcid.org/0000-0001-6127-6308UNSPECIFIED
Gillessen-Kaesbach, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vierzig, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Green, AndrewUNSPECIFIEDorcid.org/0000-0002-1077-7417UNSPECIFIED
Heller, RaoulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buiting, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggermann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-413872
DOI: 10.1038/ejhg.2014.72
Journal or Publication Title: Eur. J. Hum. Genet.
Volume: 23
Number: 2
Page Range: S. 180 - 189
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5438
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MATERNAL UNIPARENTAL DISOMY; CLINICAL PHENOTYPE; CHROMOSOME 14Q32.2; DLK1-GTL2 LOCUS; GENE-CLUSTER; REGION; DOMAIN; EPIMUTATION; IDENTIFICATION; ISODISOMYMultiple languages
Biochemistry & Molecular Biology; Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41387

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