Biophysical classification of a <i>CACNA1D</i> de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder.

ABSTRACT:

Background

There is increasing evidence that de novo CACNA1D missense mutations inducing increased Cav1.3 L-type Ca²⁺-channel-function confer a high risk for neurodevelopmental disorders (autism spectrum disorder with and without neurological and endocrine symptoms). Electrophysiological studies demonstrating the presence or absence of typical gain-of-function gating changes could therefore serve as a tool to distinguish likely disease-causing from non-pathogenic de novo CACNA1D variants in affected individuals. We tested this hypothesis for mutation S652L, which has previously been reported in twins with a severe neurodevelopmental disorder in the Deciphering Developmental Disorder Study, but has not been classified as a novel disease mutation.

Methods<

SUBMITTER: Hofer NT 

PROVIDER: S-EPMC6950833 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature