EVIDENCE FOR GENETIC-HETEROGENEITY UNDERLYING HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES

Hereditary neuropathy with liability to pressure palsies (HNPP) is a d isorder of the peripheral nervous system, the cause of which has recen tly been identified as a deletion on chromosome 17p. The deletion corr esponds to the duplication that is commonly observed in patients with hereditary motor and sensory neuropathy type Ia (HMSNIa, 17p11.2-p12). Therefore, the gene for peripheral myelin protein 22 (PMP-22) is a ca ndidate gene for both HMSNIa and HNPP. Here, we show that a similar de letion is present in one family with HNPP but is clearly absent in ano ther family. Affected members of this family carry the expected two co pies of the PMP-22 gene and the surrounding region. Furthermore, linka ge analyses of this family exclude a large part of 17p, spanning the a rea deleted in other families with HNPP, as the location for the disea se gene. These data strongly argue for the existence of genetic hetero geneity underlying HNPP. Re suits from two-point linkage analysis with markers on chromosome Iq are inconsistent with a possible involvement of the locus for HMSNIb in the present family.