Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis.

ABSTRACT:

Objective

To identify the genetic cause of disease in a form of congenital spinal muscular atrophy and arthrogryposis (CSMAA).

Methods

A 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis, and diminished lower limb movement. Whole-exome sequencing (WES) was performed on the proband and family members. In silico modeling of protein structure and heterologous protein expression and cytotoxicity assays were performed to validate pathogenicity of the identified variant.

Results

WES revealed a homozygous mutation in the TRPV4 gene (c.281C>T; p.S94L). The identification of a recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated

SUBMITTER: Velilla J 

PROVIDER: S-EPMC6454305 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature