Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.

ABSTRACT:

Purpose

CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.

Methods

We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.

Results

Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experi

SUBMITTER: Rodan LH 

PROVIDER: S-EPMC8488020 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature