Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot–Marie–Tooth Disease Type 2

Sheng Deng, Shawna M.E. Feely, Yong Shi, Hong Zhai, Luna Zhan, Teepu Siddique, Han Xiang Deng*, Michael E. Shy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Mutations in TRPV4 are linked to a group of clinically distinct, but also overlapping axonal neuropathies, including Charcot–Marie–Tooth disease type 2C (CMT2C), scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. The incidence of TRPV4-linked cases ranges from 0 to 7% in overall axonal neuropathy cohorts from European countries and Australia. However, the data from other areas remain largely unknown. In this study, we screened for TRPV4 mutations in a well-characterized USA cohort of 62 unrelated CMT2 patients without mutations in MFN2, GARS, NEFL, and GDAP1. All 15 coding exons of TRPV4 were analyzed by Sanger-sequencing. Clinical features of TRPV4-linked patients were compared with those lacking TRPV4 mutations. We identified two TRPV4 mutations in two patients. A TRPV4-R316C was identified in a patient with family history, while a TRPV4-R269C in an apparently sporadic case. Marked clinical variations were observed in the patients with TRPV4 mutations. Our data suggest that TRPV4-linked CMT2C accounts for a sizable fraction in this USA cohort of CMT2; it has a wide phenotypic spectrum, and vocal cord paralysis, scapular weakness and wasting, skeletal dysplasia, and hearing loss are suggestive signs for TRPV4-linked CMT2C.

Original languageEnglish (US)
Pages (from-to)68-72
Number of pages5
JournalNeuromolecular medicine
Volume22
Issue number1
DOIs
StatePublished - Mar 1 2020

Keywords

  • Axonal neuropathy
  • CMT2C
  • Charcot–Marie–Tooth disease
  • TRPV4
  • Vocal cord paralysis

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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