A novel mutation of COL2A1 in a large Chinese family with avascular necrosis of the femoral head

Zeng Zhang,Zhenlin Zhang,Kechao Zhu,Qi Wang,Huiyong Dai,Changqing Zhang

doi:10.1186/s12920-021-00995-y

Abstract

Avascular necrosis of the femoral head (ANFH) is a debilitating bone disease, characterized by collapse of the femoral head and subsequent loss of hip joint function. Heterozygous mutations in COL2A1 have been identified to cause familial ANFH. Here we report on a large Chinese family with ANFH and a novel heterozygous mutation (c.3517 G > A, p.Gly1173Ser) in exon 50 of COL2A1 in the Gly-X–Y domain. Previously, only five different COL2A1 mutations have been described in patients with familial ANFH. Therefore, our findings provide significant clues to the phenotype–genotype relationships in familial ANFH and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases.

Highlights

Type II collagenopathies represent a group of chondrodysplasias which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal (Achondrogenesis II; OMIM 200610) to severe (Spondyloepiphyseal dysplasia congenital; OMIM 183900) to those with only mild arthropathy (Stickler dysplasia; OMIM 108300) [1,2,3,4]
The common molecular bases of the type II collagenopathies are heterozygous mutations in the type II collagen gene (COL2A1), which encodes the precursor of the type II collagen α1 chain, the most abundant cartilage component [5]
We screened for the Collagen type II alpha chain (COL2A1) mutation in the proband using polymerase chain reaction (PCR) followed by direct sequence analysis

Summary

Introduction

Type II collagenopathies represent a group of chondrodysplasias which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal (Achondrogenesis II; OMIM 200610) to severe (Spondyloepiphyseal dysplasia congenital; OMIM 183900) to those with only mild arthropathy (Stickler dysplasia; OMIM 108300) [1,2,3,4]. Most cases of ANFH are sporadic, and several etiologic factors (including trauma, alcohol, steroids) have been reported to be implicated [6, 7]. There are familial cases of ANFH, which may be related to genetic factors. Liu et al identified that heterozygous mutations in COL2A1 caused familial ANFH [8]. Familial ANFH belongs to type II collagenopathies and represents the mild end of spectrum

Methods

Results

Conclusion