Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia – VCP gene

Inclusive body myopathy with early-onset Paget's disease and frontotemporal dementia (IBMPFD) is a condition that can affect the muscles, bones and brain.

In general, the first symptom of this process is myopathy, which can affect the extremities, as well as the respiratory and cardiac muscles. In approximately 50% of cases affected individuals develop Paget´s disease of bone, which most often affects the bones of the hips, the spine and the skull, as well as the long bones of the arms and legs. In addition, one third of people with IBMPFD suffer from frontotemporal dementia, which is usually evident around the age of forty or fifty. People with frontotemporal dementia may initially have trouble speaking, dysnomy and dyscalculia. Over time, the condition damages parts of the brain that control reasoning, personality, social skills, speech and language.

This process is due to mutations in the VCP gene (valosin containing protein), located on the short arm of chromosome 9 (9p13.3), which encodes an enzyme called protein containing valosin, which has a wide variety of functions inside of the cells. Among them, this protein is involved in cell division, fusing cell structures once cells have split, preventing apoptosis and repairing damaged DNA. In addition, this protein is part of the ubiquitin-proteasome system that breaks down unnecessary proteins inside cells.

More than 30 mutations in the VCP gene have been identified in people with this disease. The mutations described consist of aminoacid changes that affect the protein´s ability to break down other proteins as part of the ubiquitin-proteosome system. As a result, an excess of abnormal proteins builds up in muscles, bones and brain cells that interfere with the normal functions of these cells.

This disease is inherited with an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to express the process.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia, by means of the complete PCR amplification of the exons of the VCP gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).