De novo CACNA1D Ca²⁺ channelopathies: clinical phenotypes and molecular mechanism.

ABSTRACT: The identification of rare disease-causing variants in humans by large-scale next-generation sequencing (NGS) studies has also provided us with new insights into the pathophysiological role of de novo missense variants in the CACNA1D gene that encodes the pore-forming α1-subunit of voltage-gated Cav1.3 L-type Ca²⁺ channels. These CACNA1D variants have been identified somatically in aldosterone-producing adenomas as well as germline in patients with neurodevelopmental and in some cases endocrine symptoms. In vitro studies in heterologous expression systems have revealed typical gating changes that indicate enhanced Ca²⁺ influx through Cav1.3 channels as the underlying disease-causing mechanism. Here we summarize the clinical findings of 12 well-characterized individual

SUBMITTER: Ortner NJ 

PROVIDER: S-EPMC7351864 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature