Valentijn L J, Bolhuis P A, Zorn I, Hoogendijk J E, van den Bosch N, Hensels G W, Stanton V P, Housman D E, Fischbeck K H, Ross D A
Department of Neurology, Academical Medical Center, Amsterdam, The Netherlands.
Nat Genet. 1992 Jun;1(3):166-70. doi: 10.1038/ng0692-166.
Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a DNA duplication at chromosome 17p11.2. In view of the point mutation in the gene for peripheral myelin protein pmp-22/gas-3 in Trembler mice, a murine model for CMT1A, we have analysed whether this gene is altered in CMT1A. Here we show that the human homologue of the murine pmp-22 gene is located within the CMT1A DNA duplication, which is a direct repeat and does not interrupt the coding region of PMP-22. Expression of PMP-22 in CMT1A fibroblasts is similar to expression in control fibroblasts. Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A.
1A型遗传性运动感觉神经病（CMT1A）与17号染色体p11.2处的DNA重复有关。鉴于震颤小鼠（CMT1A的一种小鼠模型）外周髓磷脂蛋白pmp - 22/gas - 3基因中的点突变，我们分析了该基因在CMT1A中是否发生改变。在此我们表明，小鼠pmp - 22基因的人类同源物位于CMT1A DNA重复区域内，该区域是一个直接重复序列，并未中断PMP - 22的编码区。CMT1A成纤维细胞中PMP - 22的表达与对照成纤维细胞中的表达相似。因此，基因剂量增加或外周神经系统中PMP - 22表达改变可能是PMP - 22参与CMT1A的机制。
