Deiman Frederik E, de Brouwer Remco, Baumhove Lukas, Bomer Nils, Grote Beverborg Niels, van der Meer Peter
Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands.
Neth Heart J. 2025 Apr;33(4):112-119. doi: 10.1007/s12471-025-01941-8. Epub 2025 Mar 6.
Phospholamban (PLN) p.Arg14del (R14del, R14) is the most commonly identified pathogenic variant that causes cardiomyopathy in the Netherlands. Many disease characteristics are still unclear, including the phenotypic triggers, disease progression and disease-specific biomarkers. We aim to gain a better understanding of the R14 pathophysiology by establishing a cohort across the R14 disease spectrum.
The Disease spECifIc PatHways and modifiERs in PhosphoLambaN r14del cardiomyopathy (DECIPHER-PLN) cohort includes 101 participants, categorised as unaffected R14 (n = 21), early affected R14 (n = 42), end-stage R14 (n = 28) and heart failure (HF) of another aetiology (n = 10). R14 category was based on left ventricular ejection fraction, HF symptoms, electrocardiogram (ECG) and N‑terminal pro-brain natriuretic peptide concentrations. Of the 91 included R14 carriers, 46 (51%) were female, with a mean age of 55 years (standard deviation: 14). Low-voltage ECG older age, arrhythmias, and conduction and repolarisation abnormalities were common in (early) affected R14 carriers. Serum and plasma were collected from all participants. Induced pluripotent stem cells were generated from fibroblasts of end-stage R14 patients and unaffected R14 family members (n = 4) and differentiated into cardiomyocytes. Explanted heart tissue was obtained from R14 patients undergoing cardiac surgery and patients with other HF aetiologies as control. Abnormal PLN protein localisation was confirmed in R14 carriers.
DECIPHER-PLN comprises R14 carriers across the disease and non-disease spectrum and can be used to identify disease-specific biological pathways and modifiers that play a role in R14 cardiomyopathy. Using a multi-omics approach and in vitro disease modelling, we aim to identify novel biomarkers and improve our understanding of R14 pathophysiology. Material is available upon request.
磷蛋白（PLN）p.Arg14del（R14del，R14）是荷兰最常见的导致心肌病的致病变异。许多疾病特征仍不明确，包括表型触发因素、疾病进展和疾病特异性生物标志物。我们旨在通过建立一个涵盖R14疾病谱的队列，更好地了解R14的病理生理学。
磷蛋白R14del心肌病的疾病特异性途径和修饰因子（DECIPHER-PLN）队列包括101名参与者，分为未受影响的R14（n = 21）、早期受影响的R14（n = 42）、终末期R14（n = 28）和其他病因的心力衰竭（HF）（n = 10）。R14类别基于左心室射血分数、HF症状、心电图（ECG）和N末端脑钠肽前体浓度。在91名纳入的R14携带者中，46名（51%）为女性，平均年龄55岁（标准差：14）。低电压ECG、老年、心律失常以及传导和复极异常在（早期）受影响的R14携带者中很常见。从所有参与者中收集血清和血浆。从终末期R14患者和未受影响的R14家族成员（n = 4）的成纤维细胞中生成诱导多能干细胞，并分化为心肌细胞。从接受心脏手术的R14患者和其他HF病因的患者中获取切除的心脏组织作为对照。在R14携带者中证实了PLN蛋白的异常定位。
DECIPHER-PLN队列涵盖了疾病和非疾病谱中的R14携带者，可用于识别在R14心肌病中起作用的疾病特异性生物途径和修饰因子。我们旨在通过多组学方法和体外疾病建模来识别新的生物标志物，并增进我们对R14病理生理学的理解。如有需要可提供材料。
