De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype

Abstract Background Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. T...

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Main Authors:	Yanrui Jiang, Huizhen Sun, Qingmin Lin, Zengge Wang, Guanghai Wang, Jian Wang, Fan Jiang, Ruen Yao
Format:	Article
Language:	English
Published:	BMC 2019-08-01
Series:	BMC Medical Genetics
Subjects:	Wolf-Hirschhorn syndrome NSD2 gene Truncating variants
Online Access:	http://link.springer.com/article/10.1186/s12881-019-0863-2

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spelling	doaj-3d460fe7000342e68bbc19398aad01ff2021-04-02T09:41:01ZengBMCBMC Medical Genetics1471-23502019-08-012011510.1186/s12881-019-0863-2De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotypeYanrui Jiang0Huizhen Sun1Qingmin Lin2Zengge Wang3Guanghai Wang4Jian Wang5Fan Jiang6Ruen Yao7Department of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of MedicineAbstract Background Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. Case presentation Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. Conclusion Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.http://link.springer.com/article/10.1186/s12881-019-0863-2Wolf-Hirschhorn syndromeNSD2 geneTruncating variants
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Yanrui Jiang Huizhen Sun Qingmin Lin Zengge Wang Guanghai Wang Jian Wang Fan Jiang Ruen Yao
spellingShingle	Yanrui Jiang Huizhen Sun Qingmin Lin Zengge Wang Guanghai Wang Jian Wang Fan Jiang Ruen Yao De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype BMC Medical Genetics Wolf-Hirschhorn syndrome NSD2 gene Truncating variants
author_facet	Yanrui Jiang Huizhen Sun Qingmin Lin Zengge Wang Guanghai Wang Jian Wang Fan Jiang Ruen Yao
author_sort	Yanrui Jiang
title	De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
title_short	De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
title_full	De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
title_fullStr	De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
title_full_unstemmed	De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype
title_sort	de novo truncating variant in nsd2gene leading to atypical wolf-hirschhorn syndrome phenotype
publisher	BMC
series	BMC Medical Genetics
issn	1471-2350
publishDate	2019-08-01
description	Abstract Background Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. Case presentation Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. Conclusion Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.
topic	Wolf-Hirschhorn syndrome NSD2 gene Truncating variants
url	http://link.springer.com/article/10.1186/s12881-019-0863-2
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De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype

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