Novel TRPV4 mutation in a large Chinese family with congenital distal spinal muscular atrophy, skeletal dysplasia and scaly skin.

Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene, encoding a polymodal Ca2+ permeable channel, have been associated with a spectrum of dominantly inherited skeletal dysplasias and neuropathies. The clinical manifestations of TRPV4-associated disorders are highly heterogeneous. This study describes a large Chinese family with a novel mutation in the TRPV4 gene. Nineteen individuals from this family were investigated. Clinical, electrophysiological, and radiographic examinations were performed. The proband and other four affected family members showed signs of congenital distal spinal muscular atrophy, skeletal abnormalities including osteonecrosis of the femoral head, and scaly skin. Based on whole-exome sequencing analysis, a novel heterozygous mutation was identified in the proband in the TRPV4 gene at position c.2355G > T, resulting in a tryptophan to cysteine substitution at amino acid 785 (p.Trp785Cys) of TRPV4. Furthermore, the mutation co-segregated with disease in this family. Thus, our findings further contributed to expansion of the clinical and phenotypic spectrum of TRPV4-associated disorders.