Clinical And Molecular Genetics Of Three Families With Hereditary Bone Disease

Hereditary osteodystrophy is a large class of bone or cartilage dysplasia disease which exist clinical and genetic heterogeneity. The clinical manifestations of the hereditary osteodystrophy are short stature, deformities, disproportionate growth and a group of skeletal dysplasia. Until now, the molecular genetic mechanisms of diseases which refer to bone and cartilage dysplasia were development rapidly. In the "The International Classification Standard of the hereditary osteodystrophy (2006)",372hereditary osteodystrophy were collected in it, which divided into37parts according to molecular genetics, biochemical and radiological characteristics, of which215have been clearly associated with single or multiple gene mutations.140causative genes have been found associated with hereditary osteodystrophy, including with fibroblast growth factor receptor3(FGFR3), type I collagen genes (COL1A2, COL1A2), type â…¡ collagen gene (COL2A1) and so on.The study were carried on clinical diagnosis, detection of disease-causing genes and the research of molecular mechanisms of the genotype-phenotype correlation referring to three pedigree suffering from hereditary osteodystrophy, which included hereditary ischemic osteonecrosis (ANFH), Legg-Calve-Perthes disease (LCPD), and osteogenesis imperfecta (OI).The disease-related genes of the first family was located in COL2A1gene by STR linkage analysis. A missense mutation (c.1888G>A, p.G1y630Ser) in exon29of COL2A1gene was further identified in7affected members, but absent in the37unaffected members from the family and completely cosegregated with two different clinical phenotype which was rare in the former reports. It was reported that the ANFH was related with type II collagen which was encoded by COL2A1gene, however we did not discover related mutations in the second family. Simultaneously, we obtained large amounts of data in the second family by exome sequencing which need further filter and analysis. It is expected to find novel genes related with the clinical phenotype in this family. The genes encoding type I collagen was reported resulting in OI, but there was not related mutations of type I collagen genes (COL1A1and COL1A2) in the third family. It was reported that IFIM5, WNT1and so on may result in OI which need further analysis. Our detailed clinical and molecular genetics research contribute to extend the gene-phenotype spectrum and the detection of disease-related genes provides the basis for prenatal genetic diagnosis and avoiding the birth of children with genetic diseases.