COL2A1 mutation (c.3508G>A) leads to avascular necrosis of the femoral head in a Chinese family: A case report

Avascular necrosis of the femoral head (ANFH) is a consequence of ischemia. Although the majority of cases of ANFH are sporadic, certain familial cases of ANFH have been reported to be associated with collagen type II α1 chain (COL2A1) mutations, which lead to COL2A1 gene dysfunction. The structure of secreted type II collagen contains a core area with a triple helical glycine (Gly)-X-Y domain, and the replacement of Gly in this region as a result of COL2A1 mutations may damage the structure of type II collagen. In the present study, a Chinese family with ANFH was recruited and genetic analysis was conducted to determine whether COL2A1 mutations were implicated in this familial ANFH. A three-generation family containing 31 members, as well as 20 patients with sporadic ANFH, were recruited for investigation. The diagnosis was performed by independent surgeons and radiologists according to internationally recognized criteria. In the present study, a heterozygous c.3508G>A mutation in exon 50 of the COL2A1 gene was identified, which results in the substitution of Gly with serine at codon 1,170. Furthermore, genetic pedigree analysis indicated that this mutation was inherited in an autosomal dominant manner. The present study revealed that a heterozygous c.3508G>A mutation in the COL2A1 gene was involved in ANFH development in one Chinese family. Therefore, it is proposed that individuals who carry this c.3508G>A mutation in the COL2A1 gene should receive genetic counseling and early intervention for ANFH.