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
| Autor: | Endres, Dominique, Decher, Niels, Röhr, Isabell, Vowinkel, Kirsty, Domschke, Katharina, Komlosi, Katalin, Tzschach, Andreas, Gläser, Birgitta, Schiele, Miriam A., Runge, Kimon, Süß, Patrick, Schuchardt, Florian, Nickel, Kathrin, Stallmeyer, Birgit, Rinné, Susanne, Schulze-Bahr, Eric, Tebartz van Elst, Ludger |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 8611, p 8611 (2020) International Journal of Molecular Sciences |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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