ABSTRACT
Hereditary neuropathy with liability to pressure palsies (HNPP) is in most cases associated with an interstitial deletion of the same 1.5-Mb region at 17p11.2 that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A) patients. Unequal crossing-over following misalignment at flanking repeat sequences (CMT1A-REP), either leads to tandem duplication in CMT1A patients or deletion in HNPP patients. With the use of polymorphic DNA markers located within the CMT1A/HNPP duplication/deletion region we detected the HNPP deletion in 16 unrelated HNPP patients, 11 of Belgian and 5 of French origin. In all cases, the 1.5-Mb size of the HNPP deletion was confirmed by EcoRI dosage analysis using a CMT1A-REP probe. In the 16 HNPP patients, the same 370/320-kb EagI deletion-junction fragments were detected with pulsed field gel electrophoresis (PFGE), while in CMT1A patients, a 150-kb EagI duplication-junction fragment was seen. Thus, PFGE analysis of EagI-digested DNA with a CMT1A-REP probe allows direct detection of the HNPP deletion or the CMT1A duplication for DNA diagnostic purposes.
Subject(s)
Chromosomes, Human, Pair 17 , Demyelinating Diseases/genetics , Peripheral Nervous System Diseases/genetics , Blotting, Southern , Charcot-Marie-Tooth Disease/genetics , Chromosome Mapping , Crossing Over, Genetic , DNA/genetics , Female , Humans , Male , Pedigree , Polymerase Chain Reaction , Restriction Mapping , Sequence DeletionABSTRACT
Hereditary neuropathy with liability to pressure palsies (NHPP) is an autosomal dominant disease of peripheral nerves, characterized by recurrent focal neuropathies often with an underlying asymptomatic polyneuropathy. We report the clinical, electrophysiological, and histopathological findings in three families with HNPP and confirm the presence of a deletion on chromosome 17p11.2, including all the markers known to be duplicated in Charcot-Marie-Tooth disease type 1A. This deletion appears to be the underlying molecular deficit in this disease and provides additional evidence for the importance of this locus for peripheral nerve function.
