title: Refined localization of dominant intermediate Charcot-Marie-Tooth neuropathy and exclusion of seven known candidate genes in the region.
abstract: Charcot-Marie-Tooth (CMT) neuropathy is one of the most common hereditary disorders of the human peripheral nervous system. The CMT syndrome includes weakness and atrophy of distal muscles, high arched feet (pes cavus), depressed or absent deep tendon reflexes, and mild sensory loss. Dominant intermediate CMT (DI-CMT) neuropathy is a form of CMT with intermediate median motor nerve conduction velocities. We previously localized the DI-CMT locus to a 16.8-cM region on chromosome 19p12-p13.2. Extended haplotype analysis and clinical assessment of additional family members and a report of a second family linked to this locus has enabled us to narrow the candidate region to a 6-cM interval flanked by D19S558 and D19S432. Selection of positional candidate genes for screening was performed on the basis of neural expression and microarray analysis of Schwann cell differentiation in vivo. Seven candidate genes have been investigated. These include six genes localized in the original linkage interval and one in the newly refined region. They are excluded as a cause for DI-CMT neuropathy.
authors.affiliation: Neurobiology Laboratory, ANZAC Research Institute, Concord Hospital, New South Wales, Australia. danqing@med.usyd.edu.au
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhu
authors.forename: Marina
authors.initials: M
authors.lastname: Kennerson
authors.forename: John
authors.initials: J
authors.lastname: Merory
authors.forename: Roman
authors.initials: R
authors.lastname: Chrast
authors.forename: Mark
authors.initials: M
authors.lastname: Verheijen
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
authors.forename: Garth
authors.initials: G
authors.lastname: Nicholson
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D005799:Genes, Dominant; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D010375:Pedigree
chemical_list: D005819:Genetic Markers