title: Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy.
abstract: Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by marked distal muscle weakness and wasting and a high frequency of foot ulcers, infections, and amputations of the toes because of recurrent infections. CMT2B maps to chromosome 3q13-q22. We refined the CMT2B locus to a 2.5-cM region and report two missense mutations (Leu129Phe and Val162Met) in the small GTP-ase late endosomal protein RAB7 which causes the CMT2B phenotype in three extended families and in three patients with a positive family history. The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues. RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, Antwerp, Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Verhoeven
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Katrien
authors.initials: K
authors.lastname: Coen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Verpoorten
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kwon
authors.forename: David
authors.initials: D
authors.lastname: FitzPatrick
authors.forename: Eric
authors.initials: E
authors.lastname: Schmedding
authors.forename: Els
authors.initials: E
authors.lastname: De Vriendt
authors.forename: An
authors.initials: A
authors.lastname: Jacobs
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Gerwen
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011994:Recombinant Proteins / Q000737:chemistry; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D011994:Recombinant Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins