A Large Chinese Family With A Novel Mutation In The TRPV4 Gene That Causes Congenital Distal SMA And Spondylometaphyseal Dysplasia

Objective: To investigate the clinical characteristics and molecular genetic mechanisms of a transient receptor potential vanilloid 4(TRPV4)ion channel disease family,rarely presented both congenital spinal muscular atrophy and skeletal dysplasia.Methods: Twenty-seven individuals including the proband from the family were investigated.Clinical evaluation,electrophysiology,medical image,blood biochemical examinations and genetic analysis of the TRPV4 gene in the family were performed.Results: A novel heterozygous mutation,was identified in the TRPV4 gene at the position c.2034G>T in the proband by whole-exome sequencing analysis,leading to an amino acid substitution of W678 C.Clinically,the proband showed signs of both congenital spinal muscular atrophy and spondylometaphyseal dysplasia.Pedigree test showed that co-segregation of this mutation in the large TRPV4 ion channel disease family.Conclusion: A novel heterozygous variant of TRPV4 gene at the position c.2034G>T is probably the pathogensis of TRPV4 ion channel disease in this family.