PuSH - Publication Server of Helmholtz Zentrum München

Popp, B.* ; Brugger, M.* ; Poschmann, S.* ; Bartolomaeus, T.* ; Radtke, M.* ; Hentschel, J.* ; di Donato, N.* ; Rump, A.* ; Gburek-Augustat, J.* ; Graf, E.* ; Wagner, M. ; Sorge, I.* ; Lemke, J.R.* ; Meitinger, T.* ; Abou Jamra, R.* ; Strehlow, V.* ; Brunet, T.

The constitutional gain-of-function variant p.Glu1099Lys in NSD2 is associated with a novel syndrome.

Clin. Genet. 103, 226-230 (2023)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
NSD2 dimethylates histone H3 at lysine 36 (H3K36me2) and is located in the Wolf-Hirschhorn syndrome (WHS) critical region. Recent descriptions have delineated loss-of-function (LoF) variants in NSD2 with a distinct disorder. The oncogenic missense variant p.Glu1099Lys occurs somatically in leukemia and has a gain-of-function (GoF) effect. We describe two individuals carrying p.Glu1099Lys as heterozygous de novo germline variant identified by exome sequencing (ES) of blood DNA and subsequently confirmed in two ectodermal tissues. Clinically, these individuals are characterized by intellectual disability, coarse/ square facial gestalt, abnormalities of the hands, and organomegaly. Public cell lines with NSD2 GoF variants had increased K36me2, DNA promoter methylation, and dysregulated RNA expression. NSD2 GoF caused by p.Glu1099Lys is associated with a novel phenotype different from WHS and Rauch-Steindl syndrome (RAUST).
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glu1099lys ; Nsd2 ; Rauch-steindl Syndrome ; Wolf-hirschhorn Syndrome ; Gain-of-function ; Neurodevelopmental Disorder
ISSN (print) / ISBN 0009-9163
e-ISSN 1399-0004
Journal Clinical Genetics
Quellenangaben Volume: 103, Issue: 2, Pages: 226-230 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Grants Deutsche Forschungsgemeinschaft