14-3-3ε Gene variants in a Japanese patient with left ventricular noncompaction and hypoplasia of the corpus callosum

摘要: Abstract Background Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by prominent trabecular meshwork and deep intertrabecular recesses, thought to be due an arrest of normal endomyocardial morphogenesis. However, the genes contributing this process remain poorly understood. 14-3-3e, encoded YWHAE, adapter protein belonging 14-3-3 family which plays important roles in neuronal development involved Miller–Dieker syndrome. We recently showed that mice lacking gene develop LVNC. Therefore, we hypothesized variants YWHAE may contribute pathophysiology LVNC humans. Methods results In 77 Japanese patients with LVNC, including probands 29 families, mutation analysis direct DNA sequencing identified 7 novel variants. One them, c.− 458G > T, promoter, was familial patient hypoplasia corpus callosum. The − 458G > T variant located within regulatory CCAAT/enhancer binding (C/EBP) response element it reduced promoter activity approximately 50%. Increased inhibitory C/EBPβ isoform implicated decreasing activity. Interestingly, had previously shown key regulator YWHAE. Conclusions These data suggest contributes abnormal myocardial morphogenesis characteristic as well brain development, implicate candidate pediatric cardiomyopathies.