PMP-22 gene duplications and deletions identified in archival, paraffin-embedded sural nerve biopsy specimens: correlation to structural changes

We retrospectively analyzed paraffin-embedded sural nerve biopsy specimens from cases suspected of having dominantly inherited motor and sensory neuropathy (HMSN) or hereditary neuropathy with liability to pressure palsy (HNPP), with respect to their proportional DNA content at chromosome 17p11.2-12, encompassing the PMP-22 gene, using polymerase chain reaction (PCR). Of 19 cases in whom HMSN Ia had been suspected on clinical, neurophysiological, and histopathological grounds, 14 showed a duplication on chromosome 17p11.2-12. A deletion in the identical chromosomal region could be identified in all of the suspected cases with HNPP. In 5 cases showing neither duplication, deletion, nor a point mutation in the exons of the PMP-22 gene on heteroduplex DNA analysis, the histopathological findings strongly suggested a diagnosis of chronic inflammatory demyelinating polyneuropathy in 2 cases, and HMSN Ib, or HMSN non-a non-b, and HMSN III in 3 cases. It is shown for the first time that archival, formalin-fixed, paraffin-embedded sural nerve biopsy samples can be used for establishing the diagnosis of PMP-22 diseases, i.e., HMSN Ia and HNPP, by PCR amplification of the region coding for the PMP-22 gene.