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J Med Genet. 2017 Feb;54(2):84-86. doi: 10.1136/jmedgenet-2016-103943. Epub 2016 Jul 7.

De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia.

Author information

1
Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
2
GeneDx, Gaithersburg, Maryland, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
4
Texas Children's Hospital, Houston, Texas, USA.
5
Massachusetts General Hospital, Boston, Massachusetts, USA.
6
University of Alabama at Birmingham, Birmingham, Alabama, USA.
7
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
8
Cohen Children's Medical Center of NY, New Hyde Park, New York, USA.
9
Office of the Clinical Director, National Institutes of Health, Bethesda, Maryland, USA.
10
Undiagnosed Diseases Program, National Institutes of Health, Bethesda, Maryland, USA.
11
Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, New York, USA.
12
Department of Medicine, Columbia University Medical Center, New York, New York, USA.

Abstract

BACKGROUND:

The causes of intellectual disability (ID) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of ID.

METHODS AND RESULTS:

In this study, we performed whole exome sequencing on a large cohort of patients with ID or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. HECW2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis.

CONCLUSION:

This study implicates pathogenic genetic variants in HECW2 as potential causes of neurodevelopmental disorders in humans.

KEYWORDS:

HECW2; de novo; intellectual disability; neurodevelopmental delay; whole exome sequencing

PMID:
27389779
PMCID:
PMC5222737
DOI:
10.1136/jmedgenet-2016-103943
[Indexed for MEDLINE]
Free PMC Article

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