A novel locus for autosomal recessive peripheral neuropathy in the EGR2 region on 10q23

Am J Hum Genet. 2000 Sep;67(3):664-71. doi: 10.1086/303053. Epub 2000 Jul 27.


During our studies of Romany (Gypsy) families with hereditary motor and sensory neuropathy-Lom, we have identified a large kindred with two independently segregating autosomal recessive neuropathies. The novel disorder, named "hereditary motor and sensory neuropathy-Russe" (HMSNR), presented as a severe disabling form of Charcot-Marie-Tooth disease with prominent sensory loss, moderately reduced motor nerve conduction velocity, and a high threshold for electrical nerve stimulation. A genome scan in two branches of the large kindred detected linkage to the 10q22-q23 region containing the early growth response 2 gene (EGR2), a transcription factor with a key role in peripheral nerve myelination. The results of sequence analysis and the detection of an intragenic polymorphism allowed us to exclude EGR2 as the HMSNR gene. Further analysis done using linkage and recombination mapping refined the position of the HMSNR gene to a small interval on 10q23.2, flanked by markers D10S581 and D10S1742, telomeric to EGR2. In this interval, a conserved seven-marker haplotype is shared by all disease chromosomes, suggesting a single founder mutation. The homozygosity region is contained in bacterial-artificial-chromosome contig 1570 of the Sanger Centre physical map and has an estimated physical size of approximately 500 kb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 10 / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Early Growth Response Protein 2
  • Female
  • Founder Effect
  • Genes, Recessive / genetics*
  • Haplotypes / genetics
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats / genetics
  • Molecular Sequence Data
  • Pedigree
  • Physical Chromosome Mapping
  • Polymorphism, Genetic / genetics
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Transcription Factors

Associated data

  • GENBANK/AF139463
  • GENBANK/J04076