Chance P F, Bird T D, Matsunami N, Lensch M W, Brothman A R, Feldman G M
Division of Medical Genetics, University of Utah Medical Center, Salt Lake City 84132.
Neurology. 1992 Dec;42(12):2295-9. doi: 10.1212/wnl.42.12.2295.
Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is associated with a DNA duplication on chromosome 17, band p11.2, resulting in partial trisomy for this region in CMT1A patients. The 17p11.2 duplication may lead to the CMT1A phenotype either through disruption of a gene at the duplication breakpoint junction or by trisomic dosage and overexpression of a gene within the duplication. To test the latter model, we evaluated a patient with complete translocation trisomy 17p for signs of CMT1A. In addition to the dysmorphic features seen in trisomy 17p, a neurologic examination and electrophysiologic studies detected a demyelinating neuropathy, compatible with CMT1A. A karyotype on the patient's father found a balanced translocation [t(14;17)] with breakpoints on chromosome 17 in either band p11.1 or proximal p11.2. An analysis of the patient's DNA confirmed trisomy 17p and mapped the translocation breakpoint to a region in 17p11.2, proximal to the duplication breakpoint in CMT1A. Our observations in this patient with trisomy 17p are relevant to an understanding of the genetic mechanism in CMT1A and provide strong evidence that gene dosage through segmental trisomy for 17p11.2 results in the CMT1A phenotype.
1型遗传性运动感觉神经病A亚型（CMT1A）与17号染色体p11.2带的DNA重复有关，导致CMT1A患者该区域部分三体性。17p11.2重复可能通过破坏重复断点连接处的基因，或通过三体剂量效应以及重复区域内基因的过表达导致CMT1A表型。为了验证后一种模型，我们评估了一名17p完全易位三体患者是否有CMT1A的体征。除了17p三体所见的畸形特征外，神经系统检查和电生理研究发现了一种脱髓鞘性神经病，与CMT1A相符。对患者父亲的核型分析发现了一种平衡易位[t(14;17)]，其17号染色体的断点位于p11.1带或近端p11.2。对患者DNA的分析证实了17p三体，并将易位断点定位到17p11.2中一个位于CMT-1A重复断点近端的区域。我们对这名17p三体患者的观察结果有助于理解CMT1A的遗传机制，并提供了有力证据，即17p11.2节段性三体导致的基因剂量效应会产生CMT1A表型。
