Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group

Neuromuscul Disord. 1991;1(2):93-7. doi: 10.1016/0960-8966(91)90055-w.


Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoradiography
  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Aberrations*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • DNA / chemistry
  • DNA Probes
  • Genetic Markers
  • Genome, Human
  • Humans
  • Polymorphism, Genetic


  • DNA Probes
  • Genetic Markers
  • DNA