■肌囊肥厚型心肌病(HCM)必须与表型相似的疾病区分开来,因为临床管理和预后可能存在很大差异。无法解释的左心室肥厚患者需要早期,通过诊断或预测性基因检测确认基因诊断。我们测试了应用17基因下一代测序(NGS)小组检测HCM和HCM表型的最常见遗传原因的可行性和实用性,包括可治疗的表型,并报告检出率。由于疾病特异性治疗的可用性,因此必须鉴定甲状腺素运载蛋白心脏淀粉样变性(ATTR-CA)和法布里病(FD)。早期开始这些治疗可能会导致更好的临床结果。
■在这个国际上,多中心,横断面试点研究,在中心实验室分析了一个或多个左心室心肌节段(通过成像方法测量)中原因不明的左心室壁厚度(LVWT)增加≥13mm的心脏科门诊患者的外周血干血斑样本.NGS包括使用IlluminaNextSeq500和NovaSeq6000测序系统检测17个基因的已知剪接区和侧翼区。
■用于NGS筛查的样本于2019年5月至2020年10月在哥伦比亚的心脏病学诊所收集。巴西,墨西哥,土耳其,以色列,沙特阿拉伯。535个样本中,128个(23.9%)样本检测为与HCM或HCM表型相关的致病性/可能致病性遗传变异呈阳性,在四个样本中检测到双重致病性/可能致病性变异。在132个(24.7%)检测到的变异中,115(21.5%)变体与HCM相关,17(3.2%)变体与HCM表型相关。MYH7(n=60,11.2%)和MYBPC3(n=41,7.7%)的变异体是最常见的HCM变异体。HCM表型变体包括TTR(n=7,1.3%)和GLA(n=2,0.4%)基因中的变体。HCM或HCM表型变异患者的平均(标准差)年龄,包括TTR和GLA变体,是42.8(17.9),54.6(17.0),和69.0(1.4)年,分别。
■总诊断率为24.7%,表明筛查策略有效地识别了地理上分散的患者中最常见的HCM和HCM表型。结果强调了包括ATTR-CA(TTR变体)和FD(GLA变体)的重要性,是可以治疗的疾病,在病因不明的LVWT增加患者的鉴别诊断中。
UNASSIGNED: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes.
UNASSIGNED: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems.
UNASSIGNED: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively.
UNASSIGNED: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.