PT  - JOURNAL ARTICLE
AU  - Esther R Berko
AU  - Megan T Cho
AU  - Christine Eng
AU  - Yunru Shao
AU  - David A Sweetser
AU  - Jessica Waxler
AU  - Nathaniel H Robin
AU  - Fallon Brewer
AU  - Sandra Donkervoort
AU  - Payam Mohassel
AU  - Carsten G Bönnemann
AU  - Martin Bialer
AU  - Christine Moore
AU  - Lynne A Wolfe
AU  - Cynthia J Tifft
AU  - Yufeng Shen
AU  - Kyle Retterer
AU  - Francisca Millan
AU  - Wendy K Chung
TI  - De novo missense variants in <em>HECW2</em> are associated with neurodevelopmental delay and hypotonia
AID  - 10.1136/jmedgenet-2016-103943
DP  - 2017 Feb 01
TA  - Journal of Medical Genetics
PG  - 84--86
VI  - 54
IP  - 2
4099  - http://jmg.bmj.com/content/54/2/84.short
4100  - http://jmg.bmj.com/content/54/2/84.full
SO  - J Med Genet2017 Feb 01; 54
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.