title: X inactivation in females with X-linked Charcot-Marie-Tooth disease.
abstract: X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.
authors.affiliation: MRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. sinead.murphy@amnch.ie
authors.forename: Sinéad M
authors.initials: SM
authors.lastname: Murphy
authors.forename: Richard
authors.initials: R
authors.lastname: Ovens
authors.forename: James
authors.initials: J
authors.lastname: Polke
authors.forename: Carly E
authors.initials: CE
authors.lastname: Siskind
authors.forename: Matilde
authors.initials: M
authors.lastname: Laurà
authors.forename: Karen
authors.initials: K
authors.lastname: Bull
authors.forename: Gita
authors.initials: G
authors.lastname: Ramdharry
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Raymond P J
authors.initials: RP
authors.lastname: Murphy
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
authors.forename: Mary M
authors.initials: MM
authors.lastname: Reilly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D041321:Chromosomes, Human, X; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*; D055815:Young Adult