Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
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作者：
肩周型脊髓性肌萎缩症(SPSMA)和遗传性运动和感觉神经病IIC(HMSN IIC，也称为HMSN2C或Charcot-Marie-Tooth病2C(CMT2C))是一种表型异质性疾病，涉及不同部位的神经和肌肉。我们最初描述了一个带有SPSMA的法裔加拿大血统的新英格兰大家庭和一个带有CMT2C的英格兰和苏格兰血统的美国家庭。我们将SPSMA和CMT2C风险基因座定位在12q24.1-q24.31，两种疾病之间存在重叠区域。进一步的分析将CMT2C风险基因减少到4-Mb区域。在此，我们报道了SPSMA和CMT2C是由编码瞬时受体电位阳离子通道V亚家族成员4(TRPV4)的基因突变引起的等位基因紊乱。功能分析表明，钙通道活性增加是导致SPSMA和CMT2C突变蛋白的一个明显特征。我们的发现将TRPV4的突变与钙稳态改变和周围神经病变联系起来，暗示了这些疾病的致病机制和可能的治疗选择。
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.
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影响因子：
4.8
作者：
Suzuki, M;Mizuno, A;Imai, M
通讯作者：
Imai, M
DOI：
10.1073/pnas.1735416100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Liedtke, W;Friedman, JM
通讯作者：
Friedman, JM
影响因子：
11.2
作者：
DYCK, PJ;LITCHY, WJ;ARONSON, AE
通讯作者：
ARONSON, AE
DOI：
10.1073/pnas.0511211103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Sidhaye, VK;Güler, AD;King, LS
通讯作者：
King, LS
影响因子：
11.4
作者：
Wegierski, Tomasz;Hill, Kerstin;Walz, Gerd
通讯作者：
Walz, Gerd