Timmerman V, Löfgren A, Le Guern E, Liang P, De Jonghe P, Martin J J, Verhalle D, Robberecht W, Gouider R, Brice A, Van Broeckhoven C
Born Bunge Foundation, University of Antwerp (UIA), Department of Biochemistry, Belgium.
Hum Genet. 1996 Jan;97(1):26-34. doi: 10.1007/BF00218828.
Hereditary neuropathy with liability to pressure palsies (HNPP) is in most cases associated with an interstitial deletion of the same 1.5-Mb region at 17p11.2 that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A) patients. Unequal crossing-over following misalignment at flanking repeat sequences (CMT1A-REP), either leads to tandem duplication in CMT1A patients or deletion in HNPP patients. With the use of polymorphic DNA markers located within the CMT1A/HNPP duplication/deletion region we detected the HNPP deletion in 16 unrelated HNPP patients, 11 of Belgian and 5 of French origin. In all cases, the 1.5-Mb size of the HNPP deletion was confirmed by EcoRI dosage analysis using a CMT1A-REP probe. In the 16 HNPP patients, the same 370/320-kb EagI deletion-junction fragments were detected with pulsed field gel electrophoresis (PFGE), while in CMT1A patients, a 150-kb EagI duplication-junction fragment was seen. Thus, PFGE analysis of EagI-digested DNA with a CMT1A-REP probe allows direct detection of the HNPP deletion or the CMT1A duplication for DNA diagnostic purposes.
遗传性压力易感性神经病（HNPP）在大多数情况下与17p11.2处相同的1.5兆碱基区域的间质性缺失相关，该区域在1型遗传性运动感觉神经病（CMT1A）患者中发生重复。侧翼重复序列（CMT1A-REP）错配后发生不等交换，要么导致CMT1A患者出现串联重复，要么导致HNPP患者出现缺失。通过使用位于CMT1A/HNPP重复/缺失区域内的多态性DNA标记，我们在16名无亲缘关系的HNPP患者中检测到了HNPP缺失，其中11名来自比利时，5名来自法国。在所有病例中，使用CMT1A-REP探针通过EcoRI剂量分析证实了HNPP缺失的大小为1.5兆碱基。在这16名HNPP患者中，通过脉冲场凝胶电泳（PFGE）检测到相同的370/320千碱基EagI缺失连接片段，而在CMT1A患者中，则观察到一个150千碱基的EagI重复连接片段。因此，用CMT1A-REP探针进行EagI消化DNA的PFGE分析可直接检测HNPP缺失或CMT1A重复，用于DNA诊断。
