Umfang:
Online-Ressource
Inhalt:
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
Anmerkung:
International journal of molecular sciences
,
21, 22 (2020) , 8611, ISSN: 1422-0067
Sprache:
Englisch
DOI:
10.3390/ijms21228611
URN:
urn:nbn:de:bsz:25-freidok-1696188
URL:
https://doi.org/10.3390/ijms21228611
URL:
https://nbn-resolving.org/urn:nbn:de:bsz:25-freidok-1696188