title: Mutation analysis in Chariot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity.
abstract: Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy most commonly caused by a DNA duplication on chromosome 17p11.2 including the peripheral myelin protein 22 (PMP22). Point mutations in the myelin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) are also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in patients showing the axonal variant of CMT, CMT type 2 (CMT2). We here describe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CMT1 and CMTX. The novel MPZ Glu141st op mutation was associated with the axonal CMT2. We conclude that the clinical and electrophysiological heterogeneity among CMT patients carrying point mutations in MPZ and GJB1 is similar. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has been excluded as the disease causing mutation.
authors: Institute for Cell Biology, ETH Hönggerberg, Zürich, Switzerland. peter.young@cell.biol.ethz.ch
authors: P
authors: P
authors: Young
authors: K
authors: K
authors: Grote
authors: G
authors: G
authors: Kuhlenbäumer
authors: O
authors: O
authors: Debus
authors: H
authors: H
authors: Kurlemann
authors: H
authors: H
authors: Halfter
authors: H
authors: H
authors: Funke
authors: E B
authors: EB
authors: Ringelstein
authors: F
authors: F
authors: Stögbauer
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008297:Male; D018993:Myelin P0 Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012720:Severity of Illness Index
chemical_list: D017630:Connexins; D018993:Myelin P0 Protein