Mutation of COL2A1 in a Chinese Family with Presentations of Legg-Calvé-Perthes Disease
The aim of this study was to identify genetic factors and chromosomal regions contributing to osteonecrosis of the femoral head (ONFH) in a Chinese family with presentations of Legg-Calvé-Perthes Disease (LCDP). Methods: In this study, we performed whole exon sequencing of a Chinese family with LCPD for mutation detection. Ten members had ONFH in twenty-seven family members in four generations family, 5 unaffected members of the studied family and 5 normal peoples as control were underwent
... were underwent whole exome sequencing for mutation detection. Structural modeling test was applied to analyze the potential structural changes caused by the missense substitution. Results: In this Chinese family affected by LCPD, the mutation (c.3508 G>A, p. Gly1170Ser) in exon 50 of COL2A1 in the Gly-X-Y domain was present in 10 patients but absent in 5 unaffected members of the studied family and in 5 control chromosomes from unaffected individuals of matched geographical ancestry. The COL2A1 gene mutation was further validated by Sanger sequencing, confirmed that were heterozygous for the mutation. Then, we identified the p.Gly1170Ser mutation in exon 50 of COL2A1 in a Chinese family with LCPD. Conclusions: This study maps the mutation of mutation (c.3508 G>A, p. Gly1170Ser) in exon 50 of COL2A1 in the Gly-X-Y domain in a Chinese family of LCPD, which causes osteonecrosis of femoral head. Background Osteonecrosis of the femoral head (ONFH) was seen in adult and children, and the osteonecrosis of the femoral head that occurs in children was called Legg-Calvé-Perthes Disease (LCDP). Although LCPD was described over 100 years ago, its etiology is still controversial. LCPD can be associated with abnormalities in factor V Leiden mutation. Glueck et al  studied the Factor V Leiden gene mutation in children with LCPD. Gruppo et al  described a family with three-generation transmission of factor V Leiden and LCPD developed in three siblings in this family. Arruda et al  report heterozygosity for factor V Leiden was the only inherited risk factor associated with the development of LCPD. Szepesi et al  and Glueck et al  suggest that the homozygous form of Factor V Leiden mutation has some role in the clinical course of LCPD. Although it has recently been postulated that thrombophilia may have a role in the aetiology of LCPD, Hammarsjo A, Armenio M, Makitie O, Zabel B, Nordgren A, Nordenskjold M, Grigelioniene G (2015) Autosomal recessive mutations in the COL2A1 gene cause severe spondyloepiphyseal dysplasia. Clinical genetics 87 (5):496-498.