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

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


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
Issue number2
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Genetics


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