Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy withliability to pressure palsies (HNPP): Reliable detection of the CMT1A duplication and HNPP deletion using 8 microsatellite markers in 2 multiplex PCRs

Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are the most frequent inherited disorders of the peripheral nervous system. They are clinically and genetically heterogeneo us. A submicroscopic tandem duplication of 1.5 Mb in chromosome 17p11.2-12 comprising the PMP22 gene is found in 70.7% of autosomal dominant Charcot-M arie-Tooth type 1 (CMT1) patients. A reciprocal deletion is found in 87.6% of HNPP patients. The size of the typical CMT1A duplication is too small fo r classical cytogenetics and the whole region including the CMT1A-REP eleme nts is sometimes too complex for a single DNA analysis method. We present r esults of a multiplex PCR of 8 microsatellite markers with multicolour fluo rescence primer labelling followed by fragment analysis on an ABI 310 Prism analyzer to simplify the diagnostic procedure. Results for 24 patients can be obtained within 24 h. This method was applied on 92 DNA samples of unre lated patients carrying a typical CMT1A duplication previously confirmed by two colour fluorescence ii situ hybridization (FISH, probe c132G8) and Eco RI/SacI Southern blotting (probe pLR7.8). Three alleles of three different sizes were clearly detected at least once in 88 of them (95.6%). Subsequent ly this analysis was applied on 312 Czech patients and revealed a CMT1A/HNP P rearrangement in 109 out of them.