Novel valosin containing protein mutation in a Swiss family with hereditary inclusion body myopathy and dementia

Abstract

Inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia is a rare but highly penetrant autosomal dominant progressive disorder linked to mutations in valosin containing protein (VCP). Here, we characterize a novel mutation in the linker 1 domain of VCP leading to inclusion body myopathy and/or frontotemporal dementia in 3 generations of a Swiss family. A detailed history of several years of clinical follow-up and electrophysiological, radiological and pathological findings are presented. Five out of 6 individuals suffered from progressive myopathy and 2 out of 6 from frontotemporal dementia, respectively. A radiologically suspected Paget's disease of the bone could not been confirmed at autopsy. This case study illustrates that only a subset of individuals shows the full triad of the disease complex and that clinicopathological findings are - when interpreted apart from familial history - hard to distinguish from sporadic inclusion body myositis.