Phenotypic Analysis And Possible Mechanism Of A New Mutation In The COL1A1 Gene In A Family With Osteogenesis Imperfecta

[Background]Osteogenesis imperfecta(OI)is an inherited connective-tissue disease with a high degree of phenotypically and genetically heterogeneous.the primary clinical manifestation involves low bone mineral density,recurrent bone fractures and progressive bone deformities,it can also present as blue sclera,hearing deficits,dentinogenesis imperfecta and ligamentous laxity.OI can overlap with Ankylosing spondylitis(AS).Typical OI is an autosomal dominant genetic disease caused by mutations in type I collagen genes(COL1A1 and COL1A2).sillence TypeⅠ-Ⅳ is the most common classification of osteogenesis imperfecta.So far,OI and AS is extremely rare,and without genetic identification.[Objective]To identify a variant gene and analyse the phenotype in the family with OI.[Methods]We collected clinical data and extracted peripheral blood DNA of the OI family,Sanger sequencing was used to screen for mutation sites in the exon region of the proband,followed verify pathogenic mutation among other members of the pedigree.referenced Guidelines for the Association of Medical Genetics and Genomics(2015ACMG)to assess the pathogenicity of variant genes.[Results]In this study,we identified a patient with type I OI and AS whose pathogenic mechanism was a mutation in the COL1A1 gene c.2144de1C site.To verify that the mutation is the cause of the disease,Sanger sequencing was performed on other members of the family.two patients with only 0I,which the mutation of this site was consistent with the mutation site of the proband.One member with normal clinical manifestations and bone mineral density had no the genetic mutation,and the proband with OI and AS showed repeated spontaneous fractures,blue sclera,dentinogenesis imperfecta.By consulting the osteogenesis imperfect gene mutation database(http://www.le.ac.uk),it was found that no mutation at the c.2144delC site was found in the existing mutation site of the COL1A1 gene.[Conclusions]We identified that complex phenotype of OI and AS caused by mutation in type I collagen COL1A1 gene c.2144delC site for the first time,the primary clinical manifestation involves short stature,blue sclera and compression fracture of lumbar spine,expanding the genotype and phenotype spectrum of OI and AS.