The Pathogenesis Of Kozlowski-type Vertebral Metaphyseal Dysplasia Caused By De Novo Mutations In TRPV4 Gene

Objectives:Based on the clinical examination and whole exome sequencing of a child with c.2479C>G point mutation of TRPV4 gene,suspected of Kozlowski type vertebral metaphyseal dysplasia syndrome,this study investigated the expression level of this gene mutation,to understand the pathogenic mechanism of this gene mutation.Methods:Through clinical examination and whole exome sequencing analysis of the children and their parents,combined with bioinformatics analysis,RNA transcriptome sequencing analysis,construction of TRPV4 gene recombinant plasmid and transfection into cells,the expression of TRPV4 gene mutation was studied at the cellular level mechanism.Results:Whole exome sequencing detected the TRPV4 gene mutation c.2079C>G in this child.Bioinformatics analysis indicated that the mutation site was pathogenic,and the amino acid mutation site was highly conserved.The mutation resulted in the 827 th The secondary space structure of the aromatic ring of the amino acid proline is changed.After transcriptome sequencing analysis and recombinant plasmid transfection into cells,real-time quantitative PCR,Western blotting,calcium ion concentration detection and cytotoxicity experiments were performed.Decreased calcium ion concentration,gene mutation affects calcium ion channel function.Conclusions:By studying the expression mechanism of TRPV4 gene mutation c.2079C>G,it is clarified that TRPV4 gene mutation is the pathogenic cause of Kozlowski type vertebral metaphyseal dysplasia in children,and it is the genetic diagnosis and pathogenic mechanism of SMDK caused by TRPV4 gene mutation.Research provides some reference...