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

Abstract

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.

Integrated analysis of COL2A1 variant data and classification of type II collagenopathies

“…However, in 2005, Liu et al identified three families with autosomal dominant inheritance of ANFH and mapped the positions of two related mutations: p.Gly1170Ser occurred in two four‐generation and five‐generation families; and p.Gly717Ser occurred in a three‐generation family . P.Gly1170Ser was subsequently found in two Chinese families in 2014 and 2018 . Moreover, p.Gly582Ser was identified in patients with ANFH …”

“…46 P.Gly1170Ser was subsequently found in two Chinese families in 2014 and 2018. 47,95 Moreover, p.Gly582Ser was identified in patients with ANFH. 96 Legg-Calve-Perthes disease (LCPD; MIM #150600) is a form of ANFH in children; its peak incidence occurs between the ages of 4 and 8 years.…”

Identification of an IGF1 mutation (c.15+3G>A) in familial osteonecrosis of the femoral head

“…Through Hardy–Weinberg equilibrium test and haplotype analysis, Wang et al found that IGF1 polymorphism was closely related to the susceptibility to osteonecrosis of the femoral head. [ 12 ] Familial osteonecrosis of the femoral head is typically inherited as an autosomal dominant trait, [ 13 ] and thus offspring are likely to have the same genetic mutation leading to the disease. Existing gene detection techniques can be used to provide molecular prenatal diagnosis along with further genetic counseling to enable early and effective interventions and treatments.…”

Mutation of COL2A1 in a Chinese Family with Presentations of Legg-Calvé-Perthes Disease

“…[38][39][40] To date, the knowledge on the development of LCPD in humans is limited because of the vast number of mutations found in the COL2A1 gene and the variability in the clinical phenotype. [41,42] It is apparent that the process in which mutations in collagens alter connective tissues is complicated and cannot be described by one single pathway. In the future study, this pedigree can be extended by including the distal relatives of the family, which we believe can probably shed some light into the delineation of the pathological phenotype heterogeneity of this disease.…”