Heliö Krista, Mäyränpää Mikko I, Saarinen Inka, Ahonen Saija, Junnila Heidi, Tommiska Johanna, Weckström Sini, Holmström Miia, Toivonen Mia, Nikus Kjell, Hathaway Julie, Siivonen Pauli, Muona Mikko, Sistonen Johanna, Salmenperä Pertteli, Gentile Massimiliano, Paananen Jussi, Myllykangas Samuel, Alastalo Tero-Pekka, Heliö Tiina, Koskenvuo Juha
Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Front Genet. 2021 Nov 25;12:786705. doi: 10.3389/fgene.2021.786705. eCollection 2021.
Familial dilated cardiomyopathy (DCM) is a monogenic disorder typically inherited in an autosomal dominant pattern. We have identified two Finnish families with familial cardiomyopathy that is not explained by a variant in any previously known cardiomyopathy gene. We describe the cardiac phenotype related to homozygous truncating variants. This study included two probands and their relatives. All the participants are of Finnish ethnicity. Whole-exome sequencing was used to test the probands; bi-directional Sanger sequencing was used to identify the variants in probands' family members. Clinical evaluation was performed, medical records and death certificates were obtained. Immunohistochemical analysis of myocardial samples was conducted. A homozygous variant was identified altogether in six individuals, all considered to be affected. None of the nine heterozygous family members fulfilled any cardiomyopathy criteria. Heart failure was the leading clinical feature, and the patients may have had a tendency for atrial arrhythmias. This study demonstrates the significance of variants as a cause of human cardiomyopathy and highlights the importance of searching for new candidate genes when targeted gene panels do not yield a positive outcome.
家族性扩张型心肌病（DCM）是一种单基因疾病，通常以常染色体显性模式遗传。我们已经确定了两个患有家族性心肌病的芬兰家族，而任何已知的心肌病基因变异都无法解释这种疾病。我们描述了与纯合截短变异相关的心脏表型。本研究包括两名先证者及其亲属。所有参与者均为芬兰裔。采用全外显子组测序检测先证者；使用双向Sanger测序鉴定先证者家庭成员中的变异。进行了临床评估，获取了病历和死亡证明。对心肌样本进行了免疫组织化学分析。总共在六名个体中鉴定出一个纯合变异，所有这些个体均被认为患病。九名杂合家庭成员均未符合任何心肌病标准。心力衰竭是主要临床特征，患者可能有房性心律失常倾向。本研究证明了变异作为人类心肌病病因的重要性，并强调了当靶向基因panel未得出阳性结果时寻找新候选基因的重要性。
