Mutation Screening For Causative Gene In A Vascular Ehler-Danlos Syndrome Family

Ehler-Danlos Syndrome is a group of inherited connective tissue disorders caused by the abnormal biosynthesis and degradation of some components in the connective tissue, such as collagen, elastic protein or glycosaminoglycan. The incidence of EDS is1/25,000, EDS type â…£ makes up under5%of cases.Vascular EDS, also known as EDS type â…£ (OMIM130050) is defined by frequent bleeding tendency, thin skin, repeated pneumothrorax and joint dislocation.The leading cause of death is arterial rupture which is unpredictable and accounts for70%of death. The Vascular Ehler-Danlos syndrome is a hereditary, autosomal dominant disease that with household heredity.COL3A1(collagen, type â…¢, alpha1, OMIM120180) gene located at2q32.2, linkage analyses have demonstrated that Vascular EDS co-segregates with polymorphic markers in this locus by Nicholls AC in1988. It confirmed that the locus may be the pathogenic sites of Vascular EDS. In a patient with type â…£ Ehlers-Danlos syndrome, Tromp et al.(1989) found substitution of serine for glycine-790in type â…¢ collagen. The mutation probably made the procollagen molecule unusually sensitive to proteases because it caused local unfolding of the triple helix. The gene contains51exons distributed over44kb, encodes the procollagen of type â…¢ collagen. The mutations within COL3A1gene result in the disorder of type â…¢ procollagen, vascular changes in physical property, lower distensibility and vascular rupture. It is reasonable that COL3Algene mutations is likely to lead to Vascular EDS.In this research, we select one pedigree (3patients in all) with Vascular Ehler-Danlos syndrome and239normal individual in Chinese Han population, using PCR amplification and direct sequencing analysis their coding region of COL3A1gene sequences. We summarize the reported hotspot exons,which have amplified and sequenced for mutations associated with Vascular EDS. We detected a missense mutation c.2176G>C in this family, which lead substitution glycine for arginine-726in type â…¢ collagen. The proband (â…¡14) and patients (â…¡5,â…¢13) and another family member â…£1are carrying. We then take239normal individuals as normal controls but failed to find the mutation c.2176G>C. The mutation and the disease phenotype were isolated. Human Gene Mutation Database (HGMD) found no missense mutation c.2176G>C included, the gene sequence databases (GeneBank) returned a number for the mutation sequence after we sent it. The number is KC567894.The study shows that the heterozygote mutation c.2176G>C in COL3A1gene result in Vascular EDS in this family, which is a new variant. Our study enrich the EDS type IV pathogenic mutation spectrum and play a positive role in diagnosis and prevention of disease.