A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease
A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease
复制标题
DOI：
10.1093/hmg/10.4.415
复制
发表时间：
2001-02-15
影响因子：
3.5
通讯作者：
Claustres, M
中科院分区：
文献类型：
--
作者：
Guilbot, A;Williams, A;Claustres, M
腓骨肌萎缩症（CMT）是一组异质性遗传性外周运动和感觉神经病变，其特征是慢性远端无力伴进行性肌肉萎缩和远端肢体感觉丧失。遗传可以是常染色体显性遗传、X连锁遗传或常染色体隐性遗传（ARCMT）。最近，在一个黎巴嫩血缘大家庭中，一个负责脱髓鞘形式的ARCMT疾病的位点（命名为CMT 4F）已被定位在19 q13上。L-和S-周蛋白是髓鞘化雪旺细胞的蛋白质，并且纯合周蛋白缺失小鼠在外周神经系统中显示出广泛的有髓纤维脱髓鞘，这表明周蛋白基因是ARCMT疾病的良好候选基因。将编码周轴蛋白（PRX）的人类基因定位于CMT 4F候选区间的19 q13。在描述了人PRX基因的特征后，我们在黎巴嫩家族中发现了一个与CMT共分离的无义R196 X突变，对一名患者的腓肠神经活检的组织学和免疫组化分析显示了与小鼠突变体的共同特征，并且没有来自髓鞘的L-周蛋白。这些数据证实了周蛋白对正常雪旺细胞功能的重要性，并证实了周蛋白缺失小鼠作为ARCMT疾病模型的实用性。
Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies characterized by chronic distal weakness with progressive muscular atrophy and sensory loss in the distal extremities. Inheritance can be autosomal dominant, X-linked or autosomal recessive (ARCMT), Recently, a locus responsible for a demyelinating form of ARCMT disease, named CMT4F, has been mapped on 19q13 in a large consanguineous Lebanese family. L- and S-periaxin are proteins of myelinating Schwann cells and homozygous periaxin-null mice display extensive demyelination of myelinated fibers in the peripheral nervous system, which suggests that the periaxin gene is a good candidate gene for an ARCMT disease. The human gene encoding the periaxins (PRX) was mapped to 19q13, in the CMT4F candidate interval. After characterizing the human PRX gene, we identified a nonsense R196X mutation in the Lebanese family which cosegregated with CMT, Histopathological and immunohistochemical analysis of a sural nerve biopsy of one patient revealed common features with the mouse mutant and the absence of L-periaxin from the myelin sheath. These data confirm the importance of the periaxin proteins to normal Schwann cell function and substantiate the utility of the periaxin-null mouse as a model of ARCMT disease.