Journal article
Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2
Neuromolecular medicine, Vol.22(1), pp.68-72
03/2020
DOI: 10.1007/s12017-019-08564-4
PMID: 31468327
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.
Details
- Title: Subtitle
- Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2
- Creators
- Sheng Deng - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaShawna M E Feely - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USAYong Shi - The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAHong Zhai - The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USALuna Zhan - The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USATeepu Siddique - The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAHan-Xiang Deng - The Ken and Ruth Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715, 303 East Chicago Avenue, Chicago, IL, 60611, USA. h-deng@northwestern.eduMichael E Shy - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. michael-shy@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Neuromolecular medicine, Vol.22(1), pp.68-72
- Publisher
- United States
- DOI
- 10.1007/s12017-019-08564-4
- PMID
- 31468327
- ISSN
- 1535-1084
- eISSN
- 1559-1174
- Grant note
- NS099623 / Foundation for the National Institutes of Health NS078287 / Foundation for the National Institutes of Health U54NS065712 / Foundation for the National Institutes of Health
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984070210702771
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