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

作者：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

来源：Nature Genetics, 2010, 42(2): 165-U102.

DOI：10.1038/ng.509

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(1,2). We mapped SPSMA and CMT2C risk loci to 12q24.1-q24.31 with an overlapping region between the two diseases(3,4). Further analysis reduced the CMT2C risk locus to a 4-Mb region(5). 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.

• 出版日期2010-2
• 单位西北大学