Left ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes and an unknown mechanism. eIF3a, an important member of the Eukaryotic translation initiation factor 3 (eIF3) family, is involved in multiple biological processes, including cell proliferation and migration during myocardial development, suggesting it could play a role in LVNC development. To investigate the association between a novel variant (c.1145 A- > G) in eIF3a and LVNC, and explore potential mechanisms that could lead to the development of LVNC. A novel eIF3a variant, c.1145 A- > G, was identified by whole-exome sequencing in a familial pedigree with LVNC. Adenovirus vectors containing wild-type eIF3a and the mutated version were constructed and co-infected into H9C2 cells. Cell proliferation, apoptosis, cell migration, and differentiation, as well as phosphorylation of ERK1/2 were studied and were measured by proliferation assays, flow cytometry, real-time PCR and Western blot, respectively. The eIF3a mutation inhibited the proliferation of H9C2 cells, induced apoptosis, promoted cell migration, and inhibited the differentiation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The effect of the eIF3a mutation may be attributed to a decrease in expression of p-ERK1/2. A novel eIF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation, differentiation, accelerated migration.This finding may provide some insight into the mechanism involved in LVNC development.

左心室致密化不全 (LVNC) 是一种异质性疾病，其遗传原因和机制不明。eIF3a 是真核翻译起始因子 3 (eIF3) 家族的重要成员，参与多种生物学过程，包括心肌发育过程中的细胞增殖和迁移，表明它可能在 LVNC 发育中发挥作用。研究 eIF3a 中的一个新变体 (c.1145 A-> G) 与 LVNC 之间的关联，并探索可能导致 LVNC 发展的潜在机制。通过全外显子组测序在 LVNC 家族谱系中鉴定了一种新的 eIF3a 变体，c.1145 A-> G。构建包含野生型 eIF3a 和突变版本的腺病毒载体并共感染 H9C2 细胞。细胞增殖、凋亡、细胞迁移和分化，以及 ERK1/2 的磷酸化进行了研究，并分别通过增殖测定、流式细胞术、实时 PCR 和蛋白质印迹进行了测量。eIF3a 突变抑制 H9C2 细胞的增殖，诱导细胞凋亡，促进细胞迁移，并抑制人诱导多能干细胞衍生的心肌细胞 (hiPSC-CMs) 的分化。eIF3a 突变的影响可能归因于 p-ERK1/2 表达的降低。一本小说 eIF3a 突变的影响可能归因于 p-ERK1/2 表达的降低。一本小说 eIF3a 突变的影响可能归因于 p-ERK1/2 表达的降低。一本小说eIF3a基因突变破坏了 p-ERK1/2 通路，导致心肌增殖、分化、迁移加速减少。这一发现可能为了解 LVNC 发展所涉及的机制提供一些见解。