De Novo Frameshift Variants in the Neuronal Splicing Factor NOVA2 Result in a Common C-Terminal Extension and Cause a Severe Form of Neurodevelopmental Disorder.

ABSTRACT: The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 downregulation in human neural cells. The NOVA2 variant protein s

SUBMITTER: Mattioli F 

PROVIDER: S-EPMC7118572 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature