Dominant Intermediate Charcot-Marie-Tooth Neuropathy Maps to Chromosome 19p12-p13.2

• Published in: American journal of human genetics 2001-10, Vol.69 (4), p.883-888
• Main Authors: Kennerson, M.L., Zhu, D., Gardner, R.J.M., Storey, E., Merory, J., Robertson, S.P., Nicholson, G.A.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Charcot-Marie-Tooth Disease - genetics; Chromosome 19; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Gene Frequency - genetics; Genes, Dominant - genetics; Haplotypes - genetics; Humans; Lod Score; Male; Medical sciences; Microsatellite Repeats - genetics; Molecular Sequence Data; Neurology; Pedigree; Recombination, Genetic - genetics
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/323743

The hereditary disorders of peripheral nerve form one of the most common groups of human genetic diseases, collectively called Charcot-Marie-Tooth (CMT) neuropathy. Using linkage analysis we have identified a new locus for a form of CMT that we have called “ dominant intermediate CMT” (DI-CMT). A genomewide screen using 383 microsatellite markers showed strong linkage to the short arm of chromosome 19 (maximum LOD score 4.3, with a recombination fraction (θ) of 0, at D19S221 and maximum LOD score 5.28, θ=0, at D19S226). Haplotype analysis performed with 14 additional markers placed the DI-CMT locus within a 16.8-cM region flanked by the markers D19S586 and D19S546. Multipoint linkage analysis suggested the most likely location at D19S226 (maximum multipoint LOD score 6.77), within a 10-cM confidence interval. This study establishes the presence of a locus for DI-CMT on chromosome 19p12-p13.2.