RT Journal Article
SR Electronic
T1 De novo missense variants in <em>HECW2</em> are associated with neurodevelopmental delay and hypotonia
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 84
OP 86
DO 10.1136/jmedgenet-2016-103943
VO 54
IS 2
A1 Berko, Esther R
A1 Cho, Megan T
A1 Eng, Christine
A1 Shao, Yunru
A1 Sweetser, David A
A1 Waxler, Jessica
A1 Robin, Nathaniel H
A1 Brewer, Fallon
A1 Donkervoort, Sandra
A1 Mohassel, Payam
A1 Bönnemann, Carsten G
A1 Bialer, Martin
A1 Moore, Christine
A1 Wolfe, Lynne A
A1 Tifft, Cynthia J
A1 Shen, Yufeng
A1 Retterer, Kyle
A1 Millan, Francisca
A1 Chung, Wendy K
YR 2017
UL http://jmg.bmj.com/content/54/2/84.abstract
AB 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.