Preferential X chromosome inactivation (XCI) may play an important role in the etiology of myasthenia gravis (MG), leading to the predominance of female patients in this disease, according to a new study published in Genes.

The researchers examined 121 acetylcholine receptor-positive female patients with MG and 130 age-matched controls, finding a preponderance of the skewed XCI pattern in the patients with early-onset MG.

“The present study revealed a strong increase in skewed XCI pattern in [early-onset MG] females compared to matched controls, suggesting that it can contribute to the female preponderance of the disease reported in the [early-onset MG] subgroup,” the authors wrote.

“However, despite there being an age-related increase in skewed XCI among controls, we still observed a slightly significant increase of skewed XCI in aged MG females compared to aged controls.”

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The X chromosome contains genes implicated in autoimmunity. Approximately 80% of autoimmune syndromes have female predominance, including MG, leading the research team to explore the involvement of XCI in this disease.

Serological analyses revealed that the women with MG were significantly more likely to have asymmetric inactivation of the X chromosome than the healthy women in the study, as has also been found in conditions such as autoimmune thyroiditis, scleroderma, rheumatoid arthritis, and multiple sclerosis. In particular, younger women with MG had a significantly increased preferential XCI pattern compared to healthy women, suggesting an essential contribution of skewed XCI in early-onset cases of MG.

The authors caution that, given that this is the first study revealing preferential XCI in MG and the fact that all the women in the cohort were on treatment with steroids and some were taking other medications, further studies are required to be able to rule out any pharmacological contribution to the results obtained.


Nicolì V, Tabano SM, Colapietro P, et al. Preferential X chromosome inactivation as a mechanism to explain female preponderance in myasthenia gravis. Genes. 2022;13(4):696. doi:10.3390/genes13040696