A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromes

Mutations in valosin-containing protein (VCP) are associated with a syndromic constellation of inclusion body myositis, Paget's disease of bone and frontotemporal dementia. Here we describe the case reports of two patients with a novel variation (p.I27V) in the VCP gene that was not identified in a healthy control population. One patient presented with a frontotemporal dementia syndrome associated with raised serum alkaline phosphatase and a family history of progressive muscle disease and behavioural decline, while the second patient presented with isolated progressive dysarthria. Together these cases suggest a potential for the same VCP mutation to produce distinct patterns of brain damage, underlining the clinical heterogeneity of VCP-associated disease.