MOLECULAR DIAGNOSIS OF PMP22-ASSOCIATED NEUROPATHIES USING FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) ON ARCHIVAL PERIPHERAL-NERVE TISSUE PREPARATIONS

Charcot-Marie-Tooth (CMT) syndrome type 1 and tomaculous neuropathy, a lso called hereditary neuropathy with liability to pressure palsies (H NPP), represent two groups of neurological disorders with different su btypes, which can be distinguished at the molecular level. It is known that a 1.5-mb region on chromosome 17p11.2-12, which includes the gen e for the peripheral myelin protein 22 kDa (PMP22), is duplicated in m ore than 95% of patients with CMT type 1A (CMT1A; gene dosage 3) and i s deleted in about 90% of subjects suffering from HNPP (gene dosage 1) . This duplication/deletion can be detected reliably by interphase-two -color fluorescence in situ hybridization (FISH), We report here a tec hnique for extraction of nuclei from paraffin-embedded and cryofixed s ural nerve biopsies for precise molecular diagnosis. employing interph ase-two-color FISH in clinically diagnosed CMT1 or HNPP patients. Foll owing this technique we were able to identify six CMT1A duplications i n 13 clinically diagnosed CMT1 cases and five HNPP deletions in 6 clin ically diagnosed HNPP cases; 8 control persons were included in this s tudy. This is the first report on the use of FISH in the detection of 17p11.2-12 duplication and deletion in archival biopsy material.