PCR-based strategy for the diagnosis of hereditary neuropathy with liability to pressure palsies and Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are inherited peripheral neuropathies. In most cases these disorders are caused by either the duplication (in CMT1A) or the deletion (in HNPP) of a 1.5-megabase DNA fragment on chromosome 17p11.2, which contains the peripheral myelin protein 22 gene (PMP22). We developed a rapid and simple quantitative PCR assay for the detection of the CMT1A duplication or the HNPP deletion. The assay is based on the quantitative determination of the copy number of a 240-base pair DNA fragment from exon 4 of the PMP22 gene. Quantification was done on an automated fluorescence sequencer. Using this method we analyzed four families with the HNPP phenotype. In these families we identified the deletion in all affected individuals. To test the validity of the method, we compared the quantitative PCR results from 50 DNA samples, including 15 samples from individuals with HNPP, 15 samples from CMT1A patients, and 20 from normal controls, with the results obtained by Southern blot analysis. Concordant results were obtained in 49 of the 50 cases.