DETECTION OF DELETION WITHIN 17P11.2 IN 7 FRENCH FAMILIES WITH HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES (HNPP)

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant peripheral neuropathy which is characterized by rec urrent episodes of truncular palsies. We have analyzed the D17S122 loc us in 7 French families, including 18 affected members, with microsate llite RM11GT and the RFLP probe VAW409R3a. Only one allele could be de tected in all affected individuals with the highly polymorphic RM11GT marker. Allele segregation at D17S122 showed no contribution from the affected parent to the affected child, demonstrating that an interstit ial deletion within the 17p11.2 region is associated with HNPP in the 7 families studied. This same region is duplicated, however, in anothe r inherited neuropathy, Charcot-Marie-Tooth 1A disease. This would be the first example of two dominantly inherited diseases caused by a 'in mirror image' deletion/duplication mechanism where a gene dosage effe ct would be sufficient to produce two different phenotypes characteriz ed by abnormal myelination of the peripheral nerves. The RM11GT micros atellite is an informative tool for the molecular diagnosis of HNPP.