title: Linkage and mutation analysis in an extended family with Charcot-Marie-Tooth disease type 1B.
abstract: Charcot-Marie-Tooth disease type 1 (CMT1) or hereditary motor and sensory neuropathy type I (HMSNI) is an autosomal dominant peripheral neuropathy. In most families the disease segregates with a 1.5 Mb duplication on chromosome 17p11.2 (CMT1A). A few patients have been found with point mutations in the PMP-22 gene. In some families linkage has been found with markers located on chromosome 1q21-q25 (CMT1B) and more recently mutations have been identified in the P0 gene. We analysed an extended CMT1 pedigree (CMT-B) without the CMT1A duplication. Significant positive linkage with chromosome 1 indicated that this family is of the CMT1B subtype. Sequencing of the candidate gene P0 located in chromosome band 1q21-q23 showed a C to A point mutation at position 446 in exon 3 resulting in an Asp134Glu substitution. Since the P0 mutation cosegregated with CMT1 disease we suggest that this mutation is the primary genetic cause of CMT1B in family CMT-B.
authors.affiliation: Laboratory of Neurogenetics, Born Bunge Foundation (BBS), University of Antwerp, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Nelis
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: L
authors.initials: L
authors.lastname: Muylle
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D017931:DNA Primers; D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human; D004247:DNA