Cargando…

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

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-f...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696251/
https://www.ncbi.nlm.nih.gov/pubmed/33203140
http://dx.doi.org/10.3390/ijms21228611
_version_ 1783615367420051456
author 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
author_facet 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
author_sort Endres, Dominique
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7696251
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76962512020-11-29 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, 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 Int J Mol Sci Case Report 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. MDPI 2020-11-15 /pmc/articles/PMC7696251/ /pubmed/33203140 http://dx.doi.org/10.3390/ijms21228611 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696251/
https://www.ncbi.nlm.nih.gov/pubmed/33203140
http://dx.doi.org/10.3390/ijms21228611
work_keys_str_mv AT endresdominique newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT decherniels newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT rohrisabell newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT vowinkelkirsty newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT domschkekatharina newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT komlosikatalin newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT tzschachandreas newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT glaserbirgitta newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT schielemiriama newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT rungekimon newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT sußpatrick newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT schuchardtflorian newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT nickelkathrin newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT stallmeyerbirgit newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT rinnesusanne newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT schulzebahreric newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation
AT tebartzvanelstludger newcav12channelopathywithhighfunctioningautismaffectivedisorderseveredentalenameldefectsashortqtintervalandanovelcacna1clossoffunctionmutation