PDF(Pubmed)
Abstract：
UNASSIGNED: Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).
UNASSIGNED: All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.
UNASSIGNED: A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family.
UNASSIGNED: Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.
UNASSIGNED: All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.
UNASSIGNED: A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants -8 of 54 (14.8%) -have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 -7.37; p <0.001) per variant after adjustment for sex, age, and family.
UNASSIGNED: Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.
摘要：
■左心室致密化不全（LVNC）心肌病是一种可并发心力衰竭的疾病，心律失常,血栓栓塞,和心源性猝死.这项研究的目的是在大量表型良好的俄罗斯LVNC患者中阐明LVNC的遗传景观，包括48个家庭（n=214）。
■所有指标患者都接受了临床检查和遗传分析，以及同意参与临床研究和/或基因检测的家庭成员。基因检测包括根据ACMG指南的下一代测序和基因分类。
■共鉴定出24个基因中54个致病和可能致病变异的55个等位基因，在MYH7和TTN基因中数量最多。先前在其他人群中未描述过54个中的8个变体（14.8％）的显着比例，并且可能对俄罗斯的LVNC患者具有特异性。在LVNC患者中，与射血分数保留的孤立LVNC相比,每个后续变体的存在与更严重LVNC亚型的几率增加相关.调整性别后，每个变体的相应比值比为2.77（1.37-7.37；p<0.001），年龄,和家庭。
■总的来说，LVNC患者的遗传分析，伴有心肌病相关家族史分析，导致89.6%的高诊断率。这些结果表明，遗传筛查应应用于LVNC患者的诊断和预后。
■所有指标患者都接受了临床检查和遗传分析，以及同意参与临床研究和/或基因检测的家庭成员。基因检测包括根据ACMG指南的下一代测序和基因分类。
■共鉴定出24个基因中54个致病和可能致病变异的55个等位基因，在MYH7和TTN基因中数量最多。先前在其他人群中未描述过54个中的8个变体（14.8％）的显着比例，并且可能对俄罗斯的LVNC患者具有特异性。在LVNC患者中，与射血分数保留的孤立LVNC相比,每个后续变体的存在与更严重LVNC亚型的几率增加相关.调整性别后，每个变体的相应比值比为2.77（1.37-7.37；p<0.001），年龄,和家庭。
■总的来说，LVNC患者的遗传分析，伴有心肌病相关家族史分析，导致89.6%的高诊断率。这些结果表明，遗传筛查应应用于LVNC患者的诊断和预后。
