De novo loss-of-function variants in NSD2 ( WHSC1 ) associate with a subset of Wolf-Hirschhorn syndrome.

Autor:	Barrie ES; The Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, Ohio 43215, USA., Alfaro MP; The Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, Ohio 43215, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA., Pfau RB; The Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, Ohio 43215, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA., Goff MJ; Division of Genetic and Genomic Medicine., McBride KL; Division of Genetic and Genomic Medicine.; Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, Ohio 43205, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA., Manickam K; Division of Genetic and Genomic Medicine.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA., Zmuda EJ; The Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, Ohio 43215, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2019 Aug 01; Vol. 5 (4). Date of Electronic Publication: 2019 Aug 01 (Print Publication: 2019).
DOI:	10.1101/mcs.a004044
Abstrakt:	Wolf-Hirschhorn syndrome (WHS) is a rare but recurrent microdeletion syndrome associated with hemizygosity of an interstitial segment of Chromosome 4 (4p16.3). Consistent with historical reports in which overlapping deletions defined a minimal critical region in WHS patients, recent reports from exome sequence analysis have provided further evidence that haploinsufficiency of a specific gene within this critical region, NSD2 ( WHSC1 ), is causal for many features of the syndrome. In this report, we describe three unrelated patients with loss-of-function alterations in NSD2 who presented clinically with WHS features including intrauterine growth retardation and global developmental delay. Two of the three patients also had overlapping features of failure to thrive, short stature, constipation, and hypotonia. This series adds additional cases to expand the phenotypic spectrum of WHS and reports novel NSD2 variants. (© 2019 Barrie et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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