title: Application of multiplex ligation-dependent probe analysis to define a small deletion encompassing PMP22 exons 4 and 5 in hereditary neuropathy with liability to pressure palsies.
abstract: Hereditary neuropathy with liability to pressure palsies arises as a result of defects at the chromosome 17p11.2-12 locus and in 84% of cases a 1.5 Mb deletion containing the PMP22 gene is detected by analysis that utilises polymorphic (CA)n repeat markers which flank this gene. We report the clinical and electrophysiological findings observed in a kindred with three members affected by HNPP due to a deletion containing exons 4 and 5 of the PMP22 gene. This small deletion cannot be detected using standard analysis with polymorphic (CA)n repeat markers and a definitive diagnosis was made by multiplex ligation-dependent probe analysis of PMP22 exons 1A-5. MLPA can be readily utilised as a routine diagnostic laboratory test to detect the common HNPP 1.5 Mb deletion, as well as the reciprocal 1.5 Mb insertion observed in CMT1A, but has the advantage over other diagnostic techniques of being able to define single exon deletions.
authors.affiliation: Birmingham Muscle and Nerve Centre, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. i.sutton@garvan.org.au
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Sutton
authors.forename: A Paul
authors.initials: AP
authors.lastname: Mocroft
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Lindley
authors.forename: Richard M
authors.initials: RM
authors.lastname: Barber
authors.forename: R Jane
authors.initials: RJ
authors.lastname: Bryon
authors.forename: John B
authors.initials: JB
authors.lastname: Winer
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015336:Molecular Probe Techniques; D009154:Mutation / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009431:Neural Conduction / Q000235:genetics; D010243:Paralysis / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests
chemical_list: D005819:Genetic Markers; D009185:Myelin Proteins; C073687:PMP22 protein, human