Novel PCR-based diagnostic tools for Charcot-Marie-Tooth type 1A and hereditary neuropathy with liability to pressure palsies

E A Stronach, C Clark, C Bell, A Lofgren, N G McKay, V Timmerman, C Van Broeckhoven, N E Haites

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Abstract

The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the result of DNA duplications and deletions respectively of a 1.5 Mb region on 17p11.2. The region contains the peripheral myelin protein 22 gene (PMP-22) and is flanked by homologous proximal and distal CMT1A-REP elements. The majority of duplications and deletions arise during meiotic recombination following misalignment and unequal crossing-over between the proximal and distal CMT1A-REP elements. The cross-over breakpoints are most frequently located within a 1.7 Kb hotspot of recombination and produce novel duplication or deletion junctional CMT1A-REPs with unique restriction patterns. Here we describe the use of PCR based tests, which amplify a 3.6 Kb region including the 1.7 Kb hotspot from specific CMT1A-REPs, for the rapid diagnosis of CMT1A and HNPP patients. In an analysis of 96 CMT1A and 30 HNPP patients, duplication and deletion events were detected in all samples with cross-over breakpoints known to be within the region amplified by PCR.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalJournal of the Peripheral Nervous System
Volume4
Publication statusPublished - 1999

Keywords

  • CMT1A duplication
  • HNPP deletion
  • CMT1A-REP
  • diagnosis
  • DISEASE TYPE 1A
  • RECOMBINATION HOTSPOT
  • DUPLICATION
  • CMT1A
  • DELETIONS
  • REGION
  • PMP-22
  • REPEAT

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