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.
Int J Mol Sci
; 21(22)2020 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-33203140
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
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Trastorno Autístico
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Trastornos del Humor
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Canales de Calcio Tipo L
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Esmalte Dental
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Canalopatías
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Mutación con Pérdida de Función
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania