ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.

ABSTRACT:

Abstract

Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. Ninety-seven percent of these patients carry an R206H gain-of-function point mutation in the BMP type I receptor ACVR1 (ACVR1 R206H ), which causes neofunction to Activin A and constitutively activates signaling through phosphorylated SMAD1/5/8. Although patients with FOP can harbor pathological lesions in the peripheral an

SUBMITTER: Yu X 

PROVIDER: S-EPMC9582048 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature