title: Genetic, cytogenetic and physical refinement of the autosomal recessive CMT linked to 5q31-q33: exclusion of candidate genes including EGR1.
abstract: Charcot-Marie-Tooth disease is an heterogeneous group of inherited peripheral motor and sensory neuropathies with several modes of inheritance: autosomal dominant, X-linked and autosomal recessive. By homozygosity mapping, we have identified, in the 5q23-q33 region, a third locus responsible for an autosomal recessive form of demyelinating CMT. Haplotype reconstruction and determination of the minimal region of homozygosity restricted the candidate region to a 4 cM interval. A physical map of the candidate region was established by screening YACs for microsatellites used for genetic analysis. Combined genetic, cytogenetic and physical mapping restricted the locus to a less than 2 Mb interval on chromosome 5q32. Seventeen consanguineous families with demyelinating ARCMT of various origins were screened for linkage to 5q31-q33. Three of these seventeen families are probably linked to this locus, indicating that the 5q locus accounts for about 20% of demyelinating ARCMT. Several candidate genes in the region were excluded by their position on the contig and/or by sequence analysis. The most obvious candidate gene, EGR1, expressed specifically in Schwann cells, mapped outside of the candidate region and no base changes were detected in two families by sequencing of the entire coding sequence.
authors.affiliation: INSERM U289, Hôpital de la Salpêtrière, Paris. guilbot@ccr.jussieu.fr
authors.forename: A
authors.initials: A
authors.lastname: Guilbot
authors.forename: N
authors.initials: N
authors.lastname: Ravisé
authors.forename: A
authors.initials: A
authors.lastname: Bouhouche
authors.forename: P
authors.initials: P
authors.lastname: Coullin
authors.forename: N
authors.initials: N
authors.lastname: Birouk
authors.forename: T
authors.initials: T
authors.lastname: Maisonobe
authors.forename: T
authors.initials: T
authors.lastname: Kuntzer
authors.forename: C
authors.initials: C
authors.lastname: Vial
authors.forename: D
authors.initials: D
authors.lastname: Grid
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
mesh_terms: D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors