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Introduction
Numerous factors, including trauma, alcohol, steroids, coagulation disorders, sickle cell disease and fat embolism, have been reported to be implicated in the destruction of the femoral head (1). Avascular necrosis of the femoral head (ANFH), as a consequence of impaired blood supply, is a common type II collagenopathy that is associated with collagen type II α1 chain (COL2A1) mutations (2,3). The primary clinical manifestations of ANFH are limping gait, discrepancy in leg length and pain on exertion, which have a substantial effect on the quality of life of individuals (4,5). Although the exact pathogenesis of ANFH remains to be elucidated, evidence obtained from idiopathic osteonecrosis in twin studies indicates that genetic factors may have a vital role in the development of ANFH (6,7). Additionally, genetic studies have demonstrated that various single nucleotide mutations in COL2A1 are associated with an increased risk of ANFH. Based on the data obtained from familial ANFH patients in three Chinese families, a study conducted by Liu et al (2) revealed that a G to A transition in exon 50 (c.3665G>A) or exon 30 (c.2306G>A) in COL2A1 led to the replacement of glycine (Gly) with serine at codon 1,170 in the Gly-X-Y domain among patients with ANFH, which did not occur in healthy individuals. Furthermore, a study conducted by Li et al (8) revealed that a novel p.Gly630Ser mutation in the COL2A1 gene may have led to ANFH and Legg-Calve-Perthes disease (LCPD) in a Chinese family.
The COL2A1 gene, which is localized at 12q13, encodes the necessary element for type II collagen, characterized by three homologous α1-peptide chains (9). Type II collagen is predominantly expressed in the hyaline cartilage, as well as the vitreous body and nucleus pulposus (10). Type II collagen is also an essential component of collagen in the connective tissue; the biomechanical strength of this tissue is primarily dependent on the amount and extent of collagen fibril crosslinking (11). Type II collagen is composed of three homologous α1 peptide chains (homotrimers) that twist together to form a triple-stranded helix. The triple helical domain contains ~300 amino acids, and Gly followed by two other amino acids (AAs) constitute the repeated (Gly-X-Y)n sequence. If Gly in the specific Gly-X-Y repeat is replaced by other AAs, the structure...