TRPV4 neuropathies

Abstract

Hereditary neuropathies form a clinically diverse group of disorders known for their extraordinary genetic heterogeneity. Recently, mutations in the nonselective calcium channel TRPV4 were shown to cause various dominantly inherited axonal neuropathies.1,–,3 TRP channels are cellular sensors subserving divergent roles in different organ systems in response to various chemical and physical stimuli. The normal function of TRPV4 in the peripheral nervous system, however, remains poorly understood.4 The phenotypic variability of neuropathies caused by TRPV4 mutations is extensive and includes several clinically distinct axonal neuropathy syndromes such as scapuloperoneal spinal muscular atrophy (SPSMA), Charcot-Marie-Tooth disease type 2C (CMT2C), congenital distal spinal muscular atrophy, and undifferentiated forms of axonal Charcot-Marie-Tooth disease.5 Of note, dominant TRPV4 mutations had been identified as the cause of various skeletal dysplasia syndromes.6,7 Neuropathy causing TRPV4 mutations at first seemed to be confined to a handful of highly conserved amino acids in the ankyrin …