Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy
Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy
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DOI：
10.1086/367847
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发表时间：
2003-03-01
影响因子：
9.8
通讯作者：
Timmerman, V
中科院分区：
文献类型：
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作者：
Verhoeven, K;De Jonghe, P;Timmerman, V
charcote - marie - tooth型2B （CMT2B）的临床特征是明显的远端肌肉无力和消瘦，足部溃疡、感染和因复发性感染而导致的脚趾截肢的频率很高。CMT2B定位于染色体3q13-q22。我们将CMT2B基因座定位到2.5 cm区域，并报告了小gtp酶晚期内体蛋白RAB7的两个错义突变（Leu129Phe和Val162Met），这两个突变导致了三个大家庭和三个具有阳性家族史的患者的CMT2B表型。RAB7同源物的比对表明，这两个错义突变都针对高度保守的氨基酸残基。RAB7普遍表达，我们发现在感觉和运动神经元中都有表达。
Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by marked distal muscle weakness and wasting and a high frequency of foot ulcers, infections, and amputations of the toes because of recurrent infections. CMT2B maps to chromosome 3q13-q22. We refined the CMT2B locus to a 2.5-cM region and report two missense mutations (Leu129Phe and Val162Met) in the small GTP-ase late endosomal protein RAB7 which causes the CMT2B phenotype in three extended families and in three patients with a positive family history. The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues. RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons.