De Novo Missense Variants in HECW2 Are Associated with Neurodevelopmental Delay and Hypotonia

Overview

Journal J Med Genet

Specialty Genetics

Date 2016 Jul 9

PMID 27389779

Citations 27

Authors

Esther R Berko

Megan T Cho

Christine Eng

Yunru Shao

David A Sweetser

Jessica Waxler

Nathaniel H Robin

Fallon Brewer

Sandra Donkervoort

Payam Mohassel

Carsten G Bonnemann

Martin Bialer

Christine Moore

Lynne A Wolfe

Cynthia J Tifft

Yufeng Shen

Kyle Retterer

Francisca Millan

Wendy K Chung

Affiliations

Soon will be listed here.

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.

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