Germline VWF/MPRIP and somatoplasm FGA variants synergically confer susceptibility to non-traumatic osteonecrosis of the femoral head

Abstract

Non-traumatic osteonecrosis of the femoral head (ONFH) relies on multiple pathogenic factors, including intravascular coagulation, osteoporosis and lipid metabolism disorders. Although non-traumatic ONFH has been extensively explored from various aspects, its genetic mechanism has not been fully elucidated. To identify candidate pathogenic genes responsible for non-traumatic ONFH, to explore potential roles of embryonic genetic (germline) and somatic mutations in individual susceptibility to ONFH, we performed whole-exome sequencing on tissue and blood samples from 32 patients with non-traumatic ONFH and blood samples from 30 healthy controls. Three genes might correlate with non-traumatic ONFH: VWF, MPRIP (germline mutations) and FGA (somatic mutations). Germline or somatic mutations in VWF, MPRIP and FGA correlate with intravascular coagulation and thrombosis of femoral head, consequently ischemic necrosis of the femoral head.