title: Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats.
abstract: BACKGROUND
  Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region.
  
  
  METHODS
  Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers.
  
  
  RESULTS
  In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus.
  
  
  CONCLUSIONS
  Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing.
authors.forename: Milica
authors.initials: M
authors.lastname: Gagic
authors.forename: Milica Keckarevic
authors.initials: MK
authors.lastname: Markovic
authors.forename: Miljana
authors.initials: M
authors.lastname: Kecmanovic
authors.forename: Dusan
authors.initials: D
authors.lastname: Keckarevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Mladenovic
authors.forename: Jelena
authors.initials: J
authors.lastname: Dackovic
authors.forename: Vedrana
authors.initials: V
authors.lastname: Milic-Rasic
authors.forename: Stanka
authors.initials: S
authors.lastname: Romac
mesh_terms: D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D017353:Gene Deletion; D020440:Gene Duplication / Q000235:genetics*; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human