Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies: a SacI polymorphism in the proximal CMT1A-REP elements may lead to genetic misdiagnosis

Neurogenetics. 1998 Dec;2(1):43-6. doi: 10.1007/s100480050050.

Abstract

A male patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2 by means of two-color fluorescence in situ hybridization (FISH). This duplication is typical for the vast majority of Charcot-Marie-Tooth type 1A (CMT1A) cases. Analysis of DNA extracted from peripheral blood used to detect an EcoRI/SacI 3. 2-kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication, but also revealed a 7.8-kb fragment usually observed in patients with a hereditary neuropathy with liability to pressure palsies (HNPP). Both fragments observed in one patient canot result from one unequal crossover. In EcoRI/SacI Southern hybridization experiments with probe pLR7.8 DNA of his healthy parents also revealed a 7.8-kB restriction fragment. A subsequent two-color FISH analysis, however, indicated a normal status for interphase nuclei of the parents. Hence we hypothesize that the 7.8-kb fragment observed in our patient and his parents is not the product of unequal crossover during meiosis but due to a polymorphism of the SacI site in a proximal CMT1A-REP element.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • DNA / blood
  • Deoxyribonuclease EcoRI
  • Deoxyribonucleases, Type II Site-Specific
  • Diagnostic Errors
  • Female
  • Gene Duplication
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Nuclear Family
  • Pedigree
  • Polymorphism, Restriction Fragment Length*

Substances

  • DNA
  • Deoxyribonuclease EcoRI
  • endodeoxyribonuclease SacI
  • Deoxyribonucleases, Type II Site-Specific