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

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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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