title: Denaturing high-performance liquid chromatography of the myotubularin-related 2 gene (MTMR2) in unrelated patients with Charcot-Marie-Tooth disease suggests a low frequency of mutation in inherited neuropathy.
abstract: Charcot-Marie-Tooth type 4B (CMT4B), an autosomal recessive demyelinating neuropathy characterized by focally folded myelin sheaths in the peripheral nerve, has been associated with mutations in the gene encoding myotubularin-related protein 2, MTMR2, on chromosome 11q22. To investigate whether mutations in MTMR2 may also cause different forms of CMT, we screened 183 unrelated patients with a broad spectrum of CMT and related neuropathies using denaturing high-performance liquid chromatography. We identified four frequent and three rare exonic variants; two of the rare variants were identified in two unrelated patients with congenital hypomyelinating neuropathy and not in the normal controls. Our results suggest that loss-of-function mutations in MTMR2 are preferentially associated with the CMT4B phenotype.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, England.
authors.forename: A
authors.initials: A
authors.lastname: Bolino
authors.forename: L J
authors.initials: LJ
authors.lastname: Lonie
authors.forename: M
authors.initials: M
authors.lastname: Zimmer
authors.forename: C F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: H
authors.initials: H
authors.lastname: Takashima
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D019943:Amino Acid Substitution; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005091:Exons; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor
chemical_list: D020033:Protein Isoforms; C408986:MTMR2 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor