Quantitative fluorescence-polymerase chain reaction assay for the detection of the duplication of the Charcot Marie Tooth disease type 1A critical region

Genet Test Mol Biomarkers. 2010 Apr;14(2):225-31. doi: 10.1089/gtmb.2009.0118.

Abstract

Charcot Marie Tooth (CMT) syndrome is the most common hereditary peripheral neuropathy, with an incidence of about 1 in 2500. The subtype 1A (CMT1A) is caused by a tandem duplication of a 1.5-Mb region encompassing the PMP22 gene. Conventional short tandem repeat (STR) analysis can reveal this imbalance if a triallelic pattern, defining with certainty the presence of duplication, is present. In case of duplication with a biallelic pattern, it can only indicate a semiquantitative dosage of the fluorescence intensity ratio of the two fragments. In this study we developed a quantitative fluorescence-PCR using seven highly informative STRs within the CMT1A critical region that successfully disclosed or excluded the presence of the pathogenic imbalance in a cohort of 60 samples including 40 DNAs from samples with the CMT1A duplication previously characterized with two different molecular approaches, and 20 diagnostic samples from 10 members of a five-generation pedigree segregating CMT1A, 8 unrelated cases and 2 prenatal samples. The application of the quantitative fluorescence-PCR using STRs located in the critical region could be a reliable method to evaluate the presence of the PMP22 duplication for the diagnosis and classification of hereditary neuropathies in asymptomatic subjects with a family history of inherited neuropathy, in prenatal samples in cases with one affected parent, and in unrelated patients with a sporadic demyelinating neuropathy with clinical features resembling CMT (i.e., pes cavus with hammer toes) or with conduction velocities in the range of CMT1A.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Base Sequence
  • Charcot-Marie-Tooth Disease / classification
  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / genetics*
  • DNA Primers / genetics
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Microsatellite Repeats*
  • Middle Aged
  • Myelin Proteins / genetics
  • Pedigree
  • Polymerase Chain Reaction / methods*
  • Pregnancy

Substances

  • DNA Primers
  • Genetic Markers
  • Myelin Proteins
  • PMP22 protein, human