title: Novel PCR-based diagnostic tools for Charcot-Marie-Tooth type 1A and hereditary neuropathy with liability to pressure palsies.
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.
authors.affiliation: University of Aberdeen, Department of Medical Genetics, UK. e.stronach@abdn.ac.uk
authors.forename: E A
authors.initials: EA
authors.lastname: Stronach
authors.forename: C
authors.initials: C
authors.lastname: Clark
authors.forename: C
authors.initials: C
authors.lastname: Bell
authors.forename: A
authors.initials: A
authors.lastname: Löfgren
authors.forename: N G
authors.initials: NG
authors.lastname: McKay
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003434:Crossing Over, Genetic; D020440:Gene Duplication; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D017384:Sequence Deletion
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human