New CaV1.2 channelopathy with high-functioning autism, affective disorder, severe dental enamel defects, a short QT interval, and a novel cacna1c loss-of-function mutation

Endres D, Decher N, Röhr I, Vowinkel K, Domschke K, Komlosi K, Tzschach A, Gläser B, Schiele MA, Runge K, Süß P, Schuchardt F, Nickel K, Stallmeyer B, Rinné S, Schulze-Bahr E, van Elst LT (2020)

Publication Type: Journal article

Publication year: 2020

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 21

Pages Range: 1-8

Article Number: 8611

Journal Issue: 22

DOI: 10.3390/ijms21228611

Abstract

Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.

Authors with CRIS profile

Patrick Süß Department of Molecular Neurology

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE) Philipps-Universität Marburg DE Germany (DE) Universitätsklinikum Münster DE Germany (DE)

How to cite

APA:

Endres, D., Decher, N., Röhr, I., Vowinkel, K., Domschke, K., Komlosi, K.,... van Elst, L.T. (2020). New CaV1.2 channelopathy with high-functioning autism, affective disorder, severe dental enamel defects, a short QT interval, and a novel cacna1c loss-of-function mutation. International Journal of Molecular Sciences, 21(22), 1-8. https://doi.org/10.3390/ijms21228611

MLA:

Endres, Dominique, et al. "New CaV1.2 channelopathy with high-functioning autism, affective disorder, severe dental enamel defects, a short QT interval, and a novel cacna1c loss-of-function mutation." International Journal of Molecular Sciences 21.22 (2020): 1-8.

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