Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome

Abstract

Abstract 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.

Keywords

• Usher syndrome
• MYO7A
• CALR
• Calreticulin
• Cardiomyocyte disconnection