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一种与QT间期延长和猝死相关的新型功能获得性CACNA1C变体（Gly856Asp）

A Novel Gain-of-Function CACNA1C Variant (Gly856Asp) Associated With QT Prolongation and Sudden Death.

作者信息

Tadros Rafik, Zhao Juan, Leduc Charles, Bouron-Dal Soglio Dorothée, Fournier Anne, Parent Lucie

机构信息

Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada; Montreal Heart Institute Research Centre, Montreal, Quebec, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada; Cardiovascular Genetics Centre, Montreal Heart Institute, Montreal, Quebec, Canada.

Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada; Montreal Heart Institute Research Centre, Montreal, Quebec, Canada.

出版信息

JACC Case Rep. 2025 Apr 2;30(7):103503. doi: 10.1016/j.jaccas.2025.103503.

DOI:10.1016/j.jaccas.2025.103503
PMID:40185575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12046830/
Abstract

The investigation of sudden death is challenging, but of utmost importance to guide screening in potentially at-risk relatives. We present a case of a 14-year-old boy of Central Asian ancestry with palpitations and recent sudden death of his sister. Autopsy revealed ischemic injury of uncertain etiology. Family evaluation revealed mild QT prolongation in relatives cosegregating with a novel CACNA1C variant (Gly856Asp). Functional in vitro analyses show slower inactivation kinetics (gain of function) as shown in the long QT syndrome type 8. The case highlights the importance of a holistic approach to the investigation of sudden death and screening of at-risk relatives.

摘要

猝死的调查具有挑战性，但对于指导对潜在高危亲属的筛查至关重要。我们报告了一例14岁具有中亚血统的男孩病例，他有心悸症状，其姐姐近期猝死。尸检显示存在病因不明的缺血性损伤。家族评估发现，与一种新的CACNA1C变体（Gly856Asp）共分离的亲属中有轻度QT间期延长。体外功能分析显示失活动力学较慢（功能获得），如同8型长QT综合征中所见。该病例凸显了采用整体方法调查猝死和筛查高危亲属的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/dada64747264/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/fe57e20fd16d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/12a116b2bc43/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/8a851f9243af/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/dada64747264/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/fe57e20fd16d/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/12a116b2bc43/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/8a851f9243af/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e99/12046830/dada64747264/gr3.jpg

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Novel Gain-of-Function Variant in Associated With Timothy Syndrome, Multiple Accessory Pathways, and Noncompaction Cardiomyopathy.与 Timothy 综合征、多条附加通路和心肌致密化不全相关的新型功能获得性变异体。
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8 型长 QT 综合征：CACNA1C 编码的 Cav1.2 簇中的致病变异体位于 STAC 蛋白结合位点。
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Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.Ca(V)1.2钙通道功能障碍会引发包括心律失常和自闭症在内的多系统疾病。
Cell. 2004 Oct 1;119(1):19-31. doi: 10.1016/j.cell.2004.09.011.