A genetic pedigree analysis to identify gene mutations involved in femoral head necrosis

The present study presents results from a linkage and mutation screening analysis aiming to identify the causative gene of femoral head necrosis, also known as osteonecrosis of femoral head (ONFH), in a Chinese pedigree. We collected clinical data on the osteonecrosis pedigree, and extracted blood and genomic DNA from the family members. Polymerase chain reaction (PCR) and direct sequencing allowed to identify a mutation in the COL2A1 gene of the proband; the clinical manifestations of the proband meet the criteria for osteonecrosis. The exons of COL2A1 were amplified by polymerase chain reaction and mutation screening was conducted by direct sequencing in all the family members. The locus was also sequenced in 50 unrelated healthy controls. The c.3665G>A heterozygous mutation was detected in patients of the pedigree, but not in healthy individuals. We conclude that a mutation in the COL2A1 gene is the causative agent of ONFH in this family. Therefore, this mutation may be associated with osteonecrosis in Chinese populations.