MRC Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Neuromuscul Disord. 2012 Jul;22(7):617-21. doi: 10.1016/j.nmd.2012.02.009. Epub 2012 Apr 6.
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.
X 连锁遗传性神经病（CMT1X）是第二常见的遗传性神经病，由间隙连接β-1（GJB1）基因突变引起。男性具有一致的中度严重表型，而女性具有可变的表型，这被认为是由于 X 染色体失活。我们旨在评估 CMT1X 女性的 X 染色体失活模式，并使用 CMT 检查评分将其与表型相关联，以确定 X 染色体失活模式是否解释了 CMT1X 女性的可变表型。我们使用雄激素受体检测法在 67 名 CMT1X 女性和 24 名对照中确定了 X 染色体失活模式。我们能够在 30 名女性中确定携带 GJB1 突变的 X 染色体。患者和对照组之间的 X 染色体失活模式没有差异。此外，血液中的 X 染色体失活模式与表型之间没有相关性。这些发现的一个可能解释是，施万细胞中的 X 染色体失活模式而不是血液中的 X 染色体失活模式可能解释了 CMT1X 女性的可变表型。
