IDENTICAL POINT MUTATIONS OF PMP-22 IN TREMBLER-J MOUSE AND CHARCOT-MARIE-TOOTH DISEASE TYPE-1A
IDENTICAL POINT MUTATIONS OF PMP-22 IN TREMBLER-J MOUSE AND CHARCOT-MARIE-TOOTH DISEASE TYPE-1A
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DOI：
10.1038/ng1292-288
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发表时间：
1992-12-01
期刊：
影响因子：
30.8
通讯作者：
BOLHUIS, PA
中科院分区：
文献类型：
--
作者：
VALENTIJN, LJ;BAAS, F;BOLHUIS, PA
我们研究了周围髓鞘蛋白基因，PMP-22，在一个家庭与腓骨肌萎缩症1A型（CMT 1A）。在该家系中没有CMT 1A中常见的DNA重复，但该疾病与染色体17p11.2上的CMT 1A标记VAW 409 R3之间存在强烈的连锁。我们在PMP-22中发现了一个点突变，该点突变与该疾病完全相关。突变，亮氨酸取代脯氨酸在第一个假定的跨膜结构域，是相同的，最近发现的Trembler-J小鼠。在CMT 1A家族中存在这种PMP-22缺陷以及PMP-22在与CMT 1A相关的DNA复制中的位置表明，结构改变和PMP-22的过表达都可能导致该疾病。
We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.