Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Barrie ES

PROVIDER: S-EPMC6672030 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Barrie Elizabeth S ES Alfaro Maria P MP Pfau Ruthann B RB Goff Melanie J MJ McBride Kim L KL Manickam Kandamurugu K Zmuda Erik J EJ

Cold Spring Harbor molecular case studies 20190801 4

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 ...[more]

PMID: 31171569

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Dataset Information

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

Publications

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

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