X inactivation in females with X-linked Charcot-Marie-Tooth disease.
AuthorsMurphy, Sinéad M
Siskind, Carly E
Murphy, Raymond P J
Shy, Michael E
Reilly, Mary M
AffiliationMRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. firstname.lastname@example.org
Chromosomes, Human, X
Genetic Diseases, X-Linked
X Chromosome Inactivation
MetadataShow full item record
CitationX inactivation in females with X-linked Charcot-Marie-Tooth disease. 2012, 22 (7):617-21 Neuromuscul. Disord.
PublisherNeuromuscular disorders : NMD
JournalNeuromuscular disorders : NMD
AbstractX-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.