Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, Viale del Policlinico 155, Rome, 00161, Italy.
Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
ESC Heart Fail. 2021 Jun;8(3):2310-2315. doi: 10.1002/ehf2.13260. Epub 2021 Apr 9.
We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37-year-old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, developed a dilated cardiomyopathy with ventricular tachyarrhythmias and recurrent syncope. At magnetic resonance cardiomyopathy was characterized by left ventricular dilatation with hypo-contractility and mitral prolapse with valve regurgitation. At left ventricular endomyocardial biopsy, it was documented cardiomyocyte disconnection because of cytoskeletal disorganization of cell-to-cell contacts, including intercalated discs, and mitochondrial damage and dysfunction with significant reduction of adenosine triphosphate production in patient cultured fibroblasts. At an extensive analysis by next-generation-sequencing of 4183 genes potentially related to the cardiomyopathy a pathogenic mutation of calreticulin was found. The cardiomyopathy appeared to be functionally and electrically stabilized by a combination therapy including carvedilol and amiodarone at a follow-up of 18 months.
我们报告了一种与先天性耳聋综合征相关的新型心肌病，该疾病与 MYO7A 和钙网蛋白基因的复合突变有关。一名 37 岁男性自幼患有耳聋和视力障碍（由视网膜色素变性引起），存在 MYO7A 基因突变提示先天性耳聋综合征，他出现扩张型心肌病，伴有室性心动过速和反复晕厥。磁共振成像显示左心室扩张、收缩功能减弱，二尖瓣脱垂伴瓣膜反流。左心室心肌活检显示，由于细胞间接触（包括闰盘）的细胞骨架组织紊乱，导致心肌细胞分离，以及线粒体损伤和功能障碍，患者培养的成纤维细胞中三磷酸腺苷生成显著减少。通过对 4183 个潜在与心肌病相关的基因进行下一代测序的广泛分析，发现钙网蛋白存在致病性突变。经过 18 个月的随访，卡维地洛和胺碘酮联合治疗使该患者的心肌病在功能和电生理上得到稳定。
