Clinical and molecular studies of a large family with desmin-associated restrictive cardiomyopathy

Patients with restrictive cardiomyopathy (RC) have impaired diastolic funct ion, but intact systolic function until later stages of the disease, ultima tely leading to heart failure. Primary RC is often sporadic, but also may b e inherited in an autosomal dominant fashion, particularly the idiopathic f orms. Recently there has been great interest in inherited cardiomyopathy as sociated with myocyte desmin deposition ('desminopathies'). In some such fa milies, desmin or alpha-B crystallin gene mutation is the underlying cause, and the desmin accumulation affects skeletal muscle as well, usually causi ng skeletal myopathy. We describe a large family with apparent autosomal do minant inheritance of desmin-associated RC spanning four generations, with the age of onset and severity/rate of progression being highly variable. Th is family is relatively unique in that there is no symptom-based evidence o f skeletal muscle involvement, and the known desminopathy and cardiomyopath y genes/loci have been ruled out. These data support literature suggesting that desmin deposition may be associated with different underlying gene def ects, and that a novel desminopathy gene is responsible for the condition i n this family.