Frontotemporal dementia associated with a Valosin‐Containing Protein mutation: report of three families

Objective: The phenotype of inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (FTD) (IBMPFD), associated with Valosin‐Containing Protein ( VCP ) mutations is described in 3 families. Methods: Probands were identified on the basis of a pathological diagnosis of frontotemporal lobar degeneration with neuronal intranuclear ubiquitin/TDP‐43‐positive inclusions (FTLD‐U type IV). VCP sequencing was carried out. Clinical data on affected family members were reviewed. Results: Family A: 4 subjects had a myopathy (M): 2 showed also Parkinsonism (P) and FTD. Proband's brain had FTLD‐U type IV and brainstem‐type Lewy body pathology. Muscle displayed neurogenic changes and VCP(+)‐rimmed vacuoles. A VCP R191Q mutation was found in one allele. Family B: 8 subjects developed IBMPFD: FTD was seen in 4, M in 3, P in 2 and primary progressive aphasia (PPA) in one. Proband's brain showed FTLD‐U type IV, hippocampal sclerosis (HS) as well as Lewy neurites in the substantia nigra. A novel VCP T262A mutation was found in one allele. Family C: 2 subjects developed IBMPFD. The proband had FTD while a brother presented M and dementia. Proband's brain had FTLD‐U type IV and HS. A VCP R159C mutation was found in one allele. Conclusions: We identified three new families with IBMPFD associated with VCP mutations. A novel T262A mutation was found. One individual had PPA: a novel finding in IBMPFD. Supported by AG10133