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

During our studies of Romany (Gypsy) families with hereditary motor and sen sory neuropathy-Lom, we have identified a large kindred with two independen tly segregating autosomal recessive neuropathies. The novel disorder, named "hereditary motor and sensory neuropathy-Russe" (HMSNR), presented as a se vere disabling form of Charcot-Marie-Tooth disease with prominent sensory l oss, moderately reduced motor nerve conduction velocity, and a high thresho ld for electrical nerve stimulation. A genome scan in two branches of the l arge kindred detected linkage to the 10q22-q23 region containing the early growth response 2 gene (EGR2), a transcription factor with a key role in pe ripheral nerve myelination. The results of sequence analysis and the detect ion of an intragenic polymorphism allowed us to exclude EGR2 as the HMSNR g ene. Further analysis done using linkage and recombination mapping refined the position of the HMSNR gene to a small interval on 10q23.2, flanked by m arkers D10S581 and D10S1742, telomeric to EGR2. In this interval, a conserv ed seven-marker haplotype is shared by all disease chromosomes, suggesting a single founder mutation. The homozygosity region is contained in bacteria l-artificial-chromosome contig 1570 of the Sanger Centre physical map and h as an estimated physical size of similar to 500 kb.