Grebur Kinga, Mester Balázs, Fekete Bálint András, Kiss Anna Réka, Gregor Zsófia, Horváth Márton, Farkas-Sütő Kristóf, Csonka Katalin, Bödör Csaba, Merkely Béla, Vágó Hajnalka, Szűcs Andrea
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Front Cardiovasc Med. 2024 Feb 6;11:1337378. doi: 10.3389/fcvm.2024.1337378. eCollection 2024.
The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF.
We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered "red flags".
Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups ( = 0.002) and correlated with the genotype ( = 0.457, = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found.
The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.
对于左心室射血分数（LVEF）保留的有症状左心室心肌致密化不全（LVNC）患者的基因型及其对临床表现的影响，研究较少。我们旨在描述LVEF保留的LVNC患者的遗传、心脏磁共振成像（CMR）及临床背景，以及基因型与表型的关系。
我们纳入了54例有症状的LVNC患者（LVEF：65±5%），其样本采用174基因的二代测序panel进行分析，并纳入54例对照（C）受试者。结果依据美国医学遗传学与基因组学学会的标准进行评估。提示心血管并发症风险较高的医学数据被视为“红旗标志”。
在LVNC人群中，24%携带致病性或可能致病性（P）突变；56%携带意义未明的变异（VUS）；20%未携带心肌病相关突变。关于CMR参数，LVNC组和C组有显著差异，而三个遗传亚组具有可比性。我们发现红旗标志与基因型之间存在显著关系；此外，单个受试者的红旗标志数量在遗传亚组间有显著差异（=0.002），并与基因型相关（=0.457，=0.01）。在7例儿童期诊断的LVNC患者中，有6例发现了P或VUS突变。
大量的P突变以及红旗标志与基因型之间的关联强调了在有症状的LVEF保留的LVNC患者中进行遗传辅助风险分层的重要性。
