Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head

Osteonecrosis of the femoral head is a painful and debilitating bone disease that causes bone death at the hip leading to its collapse and subsequent end-stage osteoarthritis.  The disease is poorly understood limiting treatment options to invasive surgical procedures such as total hip replacement. We have identified a Canadian family of Greek origin with osteonecrosis of the femoral head in four out of six siblings with no risk factors for the disease. Genetic analysis discovered a mutation of the TRPV4 gene found only in the four affected siblings. Measurements of the mutant protein’s function found that its activity was higher than the normal protein. TRPV4-associated phenotypes involve a large spectrum of skeletal dyscrasias and neuropathies. Our findings broaden the spectrum of phenotypes caused by TRPV4 mutations and highlight the relevance of this ion channel in the physiopathology of osteonecrosis. (By Dr Chantal Séguin, http://jmg.bmj.com/content/early/2016/06/21/jmedgenet-2016-103829 )

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Dr Chantal Séguin

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