Valentijn L J, Baas F, Wolterman R A, Hoogendijk J E, van den Bosch N H, Zorn I, Gabreëls-Festen A W, de Visser M, Bolhuis P A
Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
Nat Genet. 1992 Dec;2(4):288-91. doi: 10.1038/ng1292-288.
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.
我们对一个患有1A型夏科-马里-图斯病（CMT1A）的家族中的外周髓磷脂蛋白基因PMP - 22进行了研究。在这个家族中未发现CMT1A常见的DNA重复现象，但疾病与17号染色体p11.2上的CMT1A标记VAW409R3之间存在强连锁关系。我们在PMP - 22中发现了一个与疾病完全连锁的点突变。该突变是在第一个假定的跨膜结构域中脯氨酸取代亮氨酸，与最近在颤抖 - J小鼠中发现的突变相同。这个CMT1A家族中存在这种PMP - 22缺陷以及PMP - 22在与CMT1A相关的DNA重复区域内的位置表明，PMP - 22的结构改变和过度表达都可能导致该疾病。
