Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza. C/ Miguel Servet, 177. 50013, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) de Aragón, Av. San Juan Bosco, 13., 50009, Zaragoza, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Av. Monforte de Lemos, 3-5, 28029, Madrid, Spain.
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza. C/ Miguel Servet, 177. 50013, Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) de Aragón, Av. San Juan Bosco, 13., 50009, Zaragoza, Spain.
Mutat Res Rev Mutat Res. 2020 Oct-Dec;786:108334. doi: 10.1016/j.mrrev.2020.108334. Epub 2020 Aug 25.
Dilated cardiomyopathy is a frequent and extremely heterogeneous medical condition. Deficits in the oxidative phosphorylation system have been described in patients suffering from dilated cardiomyopathy. Hence, mutations in proteins related to this biochemical pathway could be etiological factors for some of these patients. Here, we review the clinical phenotypes of patients harboring pathological mutations in genes related to the oxidative phosphorylation system, either encoded in the mitochondrial or in the nuclear genome, presenting with dilated cardiomyopathy. In addition to the clinical heterogeneity of these patients, the large genetic heterogeneity has contributed to an improper allocation of pathogenicity for many candidate mutations. We suggest criteria to avoid incorrect assignment of pathogenicity to newly found mutations and discuss possible therapies targeting the oxidative phosphorylation function.
扩张型心肌病是一种常见且极具异质性的医学病症。患有扩张型心肌病的患者的氧化磷酸化系统存在缺陷。因此,与该生化途径相关的蛋白质的突变可能是这些患者的一些病因。在这里,我们回顾了携带编码在线粒体或核基因组中的与氧化磷酸化系统相关基因的病理性突变的扩张型心肌病患者的临床表型。除了这些患者的临床表现异质性之外,遗传异质性的多样性也导致了许多候选突变致病性的错误分配。我们提出了避免将新发现的突变错误归类为致病性的标准,并讨论了针对氧化磷酸化功能的可能治疗方法。