Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2.
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.
['Deng|Sheng|S|', 'Feely|Shawna M E|SME|', 'Shi|Yong|Y|', 'Zhai|Hong|H|', 'Zhan|Luna|L|', 'Siddique|Teepu|T|', 'Deng|Han-Xiang|HX|0000-0002-0030-8465', 'Shy|Michael E|ME|']
D000328:Adult D001369:Axons D001848:Bone Diseases, Developmental D002607:Charcot-Marie-Tooth Disease D005091:Exons D005260:Female D005817:Genetic Counseling D034381:Hearing Loss D006801:Humans D015994:Incidence D008297:Male D018908:Muscle Weakness D009134:Muscular Atrophy, Spinal D009154:Mutation D020125:Mutation, Missense D010375:Pedigree D010641:Phenotype D017354:Point Mutation D050916:TRPV Cation Channels D014481:United States D014826:Vocal Cord Paralysis
Axonal neuropathy TRPV4 CMT2C Vocal cord paralysis Charcot–Marie–Tooth disease