A FRAME-SHIFT MUTATION IN THE PMP22 GENE IN HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES

Hereditary neuropathy with liability to pressure palsies (HNPP) has be en a associated with a deletion of 1.5 megabases of chromosome 17p. On e of four biopsy proven HNPP families that we have studied did not pos sess this deletion. As the deleted DNA region includes the coding regi on for a peripheral myelin gene (PMP22), we used single strand conform ation analysis to examine this gene for mutations in the non-deleted H NPP family. An abnormal fragment in exon 1 was identified, and sequenc ing revealed a two base pair deletion in all affected family members. The deletion results in a frame shift, providing strong evidence that this gene has an important role in the pathogenesis of the disease.