%0 Journal Article %A Esther R Berko %A Megan T Cho %A Christine Eng %A Yunru Shao %A David A Sweetser %A Jessica Waxler %A Nathaniel H Robin %A Fallon Brewer %A Sandra Donkervoort %A Payam Mohassel %A Carsten G Bönnemann %A Martin Bialer %A Christine Moore %A Lynne A Wolfe %A Cynthia J Tifft %A Yufeng Shen %A Kyle Retterer %A Francisca Millan %A Wendy K Chung %T De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia %D 2017 %R 10.1136/jmedgenet-2016-103943 %J Journal of Medical Genetics %P 84-86 %V 54 %N 2 %X 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. %U https://jmg.bmj.com/content/jmedgenet/54/2/84.full.pdf