New Genetic Mutation Linked to Osteonecrosis of the Hip

Osteonecrosis or 'bone death' of the femoral head is a disease caused by interruption of blood flow in the hip bone and patients, many of whom are under the age of 25, experience pain and the bone and surrounding joint collapse.

A new genetic mutation has been discovered linked to osteonecrosis of the hip, specifically the femoral head which is the spherical-shaped mass at the top of the femur and this breakthrough could allow doctors to identify and treat the disease before symptoms arise and potentially avoid hip replacements.


Scientists at the McGill University Health Centre (Montreal, QC, Canada) obtained blood samples from affected family members to evaluate for thrombophilia markers. Blood samples or buccal smears were obtained from all affected and one non-affected family members for genomic DNA (gDNA) and processed. Candidate genes were identified by whole-exome sequencing and the transient receptor potential vanilloid 4 (TRPV4) mutation was verified by segregation analysis.

The team discovered a novel genetic mutation on a gene called TRPV4, which is known to play a critical role in blood flow control and bone cell development. Until this new discovery, only one other mutation had been identified in a few families of Asian descent and the findings have had limited potential for early diagnosis and new targeted therapy. The genetic finding was supported by identification of a TRPV4 gain of function in cultured cells.

This novel discovery could also help to better understand the biological mechanisms in the much more common form of osteonecrosis of the femoral head, namely osteonecrosis induced by the use of glucocorticoids, or more commonly, steroids. Glucocorticoids are a family of medications used worldwide as either an anti-inflammatory agent, or as an important drug in many chemotherapy regimens used to treat patients with blood cancer. It is also well known that people who are using steroid medication for various illnesses are also at risk and it is estimated that greater than 60 million people are presently taking this medication worldwide.

Chantal Séguin, MD, FRCPC, a Hematologist-Oncologist and senior author of the study said, “Osteonecrosis is a severely debilitating disease that is usually linked to identifiable risk factors such as glucocorticoid treatments, blood cancers and in some rare cases, to a genetic cause. The mutation was found to be common to all affected family members and absent in the unaffected family member, linking this new mutation to osteonecrosis. While it was known that pathogenic TRPV4 mutations affected the skeleton and the nervous system, this is the first time it has been associated with osteonecrosis of the femoral head.” The study was published on June 21, 2016, in the Journal of Medical Genetics.

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McGill University Health Centre