ClinVar

In 2 of 13 families with autosomal dominant inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD1; 167320), Watts et al. (2004) identified a C-to-T transition at nucleotide 463 of the VCP gene, resulting in an arg155-to-cys substitution (R155C).

Kim et al. (2011) identified a heterozygous R155C mutation in 3 Korean sibs with IBMPFD. The proband developed progressive dementia presenting as fluent aphasia and language difficulties with onset at age 47. She never developed myopathy, but did develop asymptomatic Paget disease with increased serum alkaline phosphatase and lytic bone lesions on imaging. Her brother developed slowly progressive proximal muscle weakness at age 50, followed by frontotemporal dementia characterized initially by comprehension defects at age 54. He never had Paget disease, although serum alkaline phosphatase was increased. A second brother developed muscle weakness at age 47, followed by Paget disease at age 53, and dementia at age 61. Brain MRI in all patients showed asymmetric atrophy in the anterior inferior and lateral temporal lobes and inferior parietal lobule with ventricular dilatation on the affected side (2 on the left, 1 on the right). Two had glucose hypometabolism in the lateral temporal and inferior parietal areas, with less involvement of the anterior temporal and frontal lobes compared to those with typical semantic dementia.