Inherited disorders linked to the X-chromosome, like haemophilia, commonly affect men, whilst carrier women are typically unaffected. X-chromosome inactivation (XCI) is a normal process in women that compensates X-doses with men, where each woman cell silences either the paternal, or maternal X, in similar proportion. Certain genetic factors skewed-XCI generating female cells preferentially silencing only one X-chromosome. Skewed-XCI in a carrier woman of an X-disorder may result in expressing symptoms when the normal gene is preferentially silenced. This paper presents a practical approach to investigate the ultimate cause of skewed-XCI, which represents an essential information for familiar genetic counselling. (https://jmg.bmj.com/content/early/2024/05/05/jmg-2024-109902 )

Authors from the Laboratory of Molecular Genetics of Haemophilia. From left to right: Betiana Ziegler, Pamela Radic, Carlos De Brasi, Liliana Rossetti and Martín Abelleyro.