Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Beygo, Jasmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Elbracht, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED de Groot, Karel UNSPECIFIED orcid.org/0000-0003-4554-9796 UNSPECIFIED Begemann, Matthias UNSPECIFIED orcid.org/0000-0002-4659-8437 UNSPECIFIED Kanber, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Platzer, Konrad UNSPECIFIED orcid.org/0000-0001-6127-6308 UNSPECIFIED Gillessen-Kaesbach, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Vierzig, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Green, Andrew UNSPECIFIED orcid.org/0000-0002-1077-7417 UNSPECIFIED Heller, Raoul UNSPECIFIED UNSPECIFIED UNSPECIFIED Buiting, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggermann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MATERNAL UNIPARENTAL DISOMY; CLINICAL PHENOTYPE; CHROMOSOME 14Q32.2; DLK1-GTL2 LOCUS; GENE-CLUSTER; REGION; DOMAIN; EPIMUTATION; IDENTIFICATION; ISODISOMY Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41387