Pfeffer Tobias J, Auber Bernd, Pabst Brigitte, Agca Kuebra C, Berliner Dominik, König Tobias, Hilfiker-Kleiner Denise, Bauersachs Johann, Ricke-Hoch Melanie
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Int J Cardiol. 2023 May 15;379:96-99. doi: 10.1016/j.ijcard.2023.03.028. Epub 2023 Mar 12.
Heat shock protein family B (small) member 6 (HSPB6) mediates cardioprotective effects against stress-induced injury. In humans two gene variants of HSPB6 have been identified with a prevalence of 1% in patients with dilated cardiomyopathy (DCM). Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease of unknown etiology in previously healthy women of whom 16-20% of PPCM carry gene variants associated with cardiomyopathy. This study was designed to analyze the prevalence of pathogenic HSPB6 gene variants in PPCM.
Whole-exome sequencing was performed in whole blood samples of PPCM patients (n = 65 PPCM patients from the German PPCM registry) and screened subsequently for HSPB6 gene variants. In this PPCM cohort one PPCM patient carries a HSPB6 gene variant of uncertain significance (VUS), which was not associated with changes in the amino acid sequence and no likely pathogenic or pathogenic variants were detected.
HSPB6 gene variants did not occur more frequently in a cohort of PPCM patients from the German PPCM registry, compared to DCM patients. Genetic analyses in larger cohorts and in cohorts of different ethiologies of PPCM patients are needed to address the role of the genetic background in the pathogenesis of PPCM.
热休克蛋白家族B（小分子）成员6（HSPB6）介导针对应激诱导损伤的心脏保护作用。在人类中，已鉴定出HSPB6的两种基因变体，在扩张型心肌病（DCM）患者中的患病率为1%。围产期心肌病（PPCM）是一种病因不明的潜在危及生命的心脏病，发生在既往健康的女性中，其中16%-20%的PPCM患者携带与心肌病相关的基因变体。本研究旨在分析PPCM中致病性HSPB6基因变体的患病率。
对PPCM患者（来自德国PPCM登记处的65例PPCM患者）的全血样本进行全外显子组测序，随后筛查HSPB6基因变体。在这个PPCM队列中，有1例PPCM患者携带意义未明的HSPB6基因变体（VUS）,其与氨基酸序列变化无关，未检测到可能致病或致病的变体。
与DCM患者相比，德国PPCM登记处的PPCM患者队列中HSPB6基因变体的出现频率并没有更高。需要在更大的队列以及不同病因的PPCM患者队列中进行基因分析，以探讨遗传背景在PPCM发病机制中的作用。
