Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4

Han Xiang Deng*, Christopher J. Klein, Jianhua Yan, Yong Shi, Yanhong Wu, Faisal Fecto, Hau Jie Yau, Yi Yang, Hong Zhai, Nailah Siddique, E. Tessa Hedley-Whyte, Robert Delong, Marco Martina, Peter J. Dyck, Teepu Siddique

*Corresponding author for this work

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166 Citations (Scopus)

Abstract

Scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (HMSN IIC, also known as HMSN2C or Charcot-Marie-Tooth disease type 2C (CMT2C)) are phenotypically heterogeneous disorders involving topographically distinct nerves and muscles. We originally described a large New England family of French-Canadian origin with SPSMA and an American family of English and Scottish descent with CMT2C. We mapped SPSMA and CMT2C risk loci to 12q24.1-q24.31 with an overlapping region between the two diseases. Further analysis reduced the CMT2C risk locus to a 4-Mb region. Here we report that SPSMA and CMT2C are allelic disorders caused by mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 4 (TRPV4). Functional analysis revealed that increased calcium channel activity is a distinct property of both SPSMA-and CMT2C-causing mutant proteins. Our findings link mutations in TRPV4 to altered calcium homeostasis and peripheral neuropathies, implying a pathogenic mechanism and possible options for therapy for these disorders.

Original languageEnglish (US)
Pages (from-to)165-169
Number of pages5
JournalNature Genetics
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2010

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Spinal Muscular Atrophy
Transient Receptor Potential Channels
Mutation
New England
Peripheral Nervous System Diseases
Mutant Proteins
Calcium Channels
Type 2C Charcot-Marie-Tooth disease
Homeostasis
Calcium
Muscles
Genes
Hereditary Motor And Sensory Neuropathy, Type IIC

ASJC Scopus subject areas

  • Genetics

Cite this

Deng, Han Xiang ; Klein, Christopher J. ; Yan, Jianhua ; Shi, Yong ; Wu, Yanhong ; Fecto, Faisal ; Yau, Hau Jie ; Yang, Yi ; Zhai, Hong ; Siddique, Nailah ; Hedley-Whyte, E. Tessa ; Delong, Robert ; Martina, Marco ; Dyck, Peter J. ; Siddique, Teepu. / Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. In: Nature Genetics. 2010 ; Vol. 42, No. 2. pp. 165-169.
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Deng, HX, Klein, CJ, Yan, J, Shi, Y, Wu, Y, Fecto, F, Yau, HJ, Yang, Y, Zhai, H, Siddique, N, Hedley-Whyte, ET, Delong, R, Martina, M, Dyck, PJ & Siddique, T 2010, 'Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4', Nature Genetics, vol. 42, no. 2, pp. 165-169. https://doi.org/10.1038/ng.509

Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. / Deng, Han Xiang; Klein, Christopher J.; Yan, Jianhua; Shi, Yong; Wu, Yanhong; Fecto, Faisal; Yau, Hau Jie; Yang, Yi; Zhai, Hong; Siddique, Nailah; Hedley-Whyte, E. Tessa; Delong, Robert; Martina, Marco; Dyck, Peter J.; Siddique, Teepu.

In: Nature Genetics, Vol. 42, No. 2, 01.02.2010, p. 165-169.

Research output: Contribution to journalArticle

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AU - Yang, Yi

AU - Zhai, Hong

AU - Siddique, Nailah

AU - Hedley-Whyte, E. Tessa

AU - Delong, Robert

AU - Martina, Marco

AU - Dyck, Peter J.

AU - Siddique, Teepu

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