Heart Failure and Familial Cardiomyopathies Unit, Cardiology Department, University Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Málaga, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28220 Madrid, Spain.
Genes (Basel). 2023 Jul 19;14(7):1468. doi: 10.3390/genes14071468.
Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the .
A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; variant in the . The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up.
We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24-59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed.
This variant is a pathogenic variant of gene that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.
致心律失常性右室心肌病（ARVC）是一种遗传性心脏病，其特征是心室心肌逐渐被纤维脂肪组织替代，这可能成为心律失常、心源性猝死甚至心力衰竭（HF）的基础。心源性猝死通常是该病的首发表现，尤其是在年轻患者中。本研究旨在描述一种新的 基因突变。
这是一项描述性观察研究，纳入了 8 个最初无关联的家族，这些家族在我们的心力衰竭和家族性心肌病单位接受随访，均为 基因中的 NM_004572.3:c.775_776insG； 变异的携带者。对索引病例进行下一代测序，对家族成员进行靶向研究时使用 Sanger 方法进行基因检测。我们收集个人和家族病史、人口统计学和临床特征、诊断时额外检查的数据以及诊断时和随访期间的心律失常事件。
共纳入 47 名患者，其中 8 名为索引病例（17%）。在所评估的家族成员中，有 16 名（34%）为该基因突变的携带者，其中 3 名也被诊断为 ARVC。大多数为女性（26 名患者；55.3%），诊断时的平均年龄为 48.9 ± 18.6 岁，中位随访时间为 39 [24-59] 个月。值得注意的是，心律失常事件作为首发表现和随访期间的表现发生率较高（分别为 21.5%和 20.9%），且 25%的样本出现心力衰竭。最常见的心室受累为右心室（4 名患者，16.7%）和双心室（4 名患者，16.7%）；我们未发现分析的任何变量存在统计学差异。
该变异是一种以前未描述过的 基因突变，也不存在于与 ARVC 相关的对照组中。它的外显率不完全，表型表达高度可变，在我们位于马拉加（西班牙安达卢西亚）的地理区域的 8 个家族中被发现，提示该区域存在一个奠基者效应，并描述了其临床和风险特征。
