Molecular genetic analysis of the 17p11.2 region in patients with hereditary neuropathy with liability to pressure palsies (HNPP)

Hum Genet. 1996 Jan;97(1):26-34. doi: 10.1007/BF00218828.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • Charcot-Marie-Tooth Disease / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • Crossing Over, Genetic
  • DNA / genetics
  • Demyelinating Diseases / genetics*
  • Female
  • Humans
  • Male
  • Pedigree
  • Peripheral Nervous System Diseases / genetics*
  • Polymerase Chain Reaction
  • Restriction Mapping
  • Sequence Deletion

Substances

  • DNA