与突变型rho鸟嘌呤核苷酸交换因子10相关的外周神经传导减慢和髓鞘变薄。
Slowed conduction and thin myelination of peripheral nerves associated with mutant rho Guanine-nucleotide exchange factor 10.
作者信息
Verhoeven Kristien, De Jonghe Peter, Van de Putte Tom, Nelis Eva, Zwijsen An, Verpoorten Nathalie, De Vriendt Els, Jacobs An, Van Gerwen Veerle, Francis Annick, Ceuterick Chantal, Huylebroeck Danny, Timmerman Vincent
机构信息
Molecular Genetics Department, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium.
出版信息
Am J Hum Genet. 2003 Oct;73(4):926-32. doi: 10.1086/378159. Epub 2003 Aug 19.
Slowed nerve-conduction velocities (NCVs) are a biological endophenotype in the majority of the hereditary motor and sensory neuropathies (HMSN). Here, we identified a family with autosomal dominant segregation of slowed NCVs without the clinical phenotype of HMSN. Peripheral-nerve biopsy showed predominantly thinly myelinated axons. We identified a locus at 8p23 and a Thr109Ile mutation in ARHGEF10, encoding a guanine-nucleotide exchange factor (GEF) for the Rho family of GTPase proteins (RhoGTPases). Rho GEFs are implicated in neural morphogenesis and connectivity and regulate the activity of small RhoGTPases by catalyzing the exchange of bound GDP by GTP. Expression analysis of ARHGEF10, by use of its mouse orthologue Gef10, showed that it is highly expressed in the peripheral nervous system. Our data support a role for ARHGEF10 in developmental myelination of peripheral nerves.
神经传导速度（NCV）减慢是大多数遗传性运动和感觉神经病（HMSN）的一种生物学内表型。在此，我们鉴定出一个家系，其常染色体显性遗传的NCV减慢，但无HMSN的临床表型。周围神经活检显示主要为薄髓鞘轴突。我们在8p23定位到一个基因座，并在ARHGEF10中发现一个苏氨酸109异亮氨酸突变，ARHGEF10编码一种针对Rho家族GTP酶蛋白（RhoGTPases）的鸟嘌呤核苷酸交换因子（GEF）。Rho GEFs参与神经形态发生和连接，并通过催化结合的GDP与GTP交换来调节小RhoGTPases的活性。利用其小鼠同源物Gef10对ARHGEF10进行表达分析，结果显示它在外周神经系统中高度表达。我们的数据支持ARHGEF10在外周神经发育性髓鞘形成中发挥作用。
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