In mammals, the potential imbalance of gene expression for the two X chromosomes in females is resolved by inactivating one X in all somatic tissues. In the embryo proper, the process of X inactivation is considered to be ... In mammals, the potential imbalance of gene expression for the two X chromosomes in females is resolved by inactivating one X in all somatic tissues. In the embryo proper, the process of X inactivation is considered to be random between the maternal and paternal chromosomes. Thus, most females have mosaic expression of maternal and paternal alleles of X chromosome loci, with a contribution of about 50% from each chromosome. However, some females show a skewed ratio of X inactivation, which can be due to negative or positive selection, or to an underlying primary genetic process. Belmont (1996) observed familial clustering of females with highly skewed patterns of X inactivation and reviewed the genetic control of X inactivation. - Genetic Heterogeneity of Skewed X Inactivation See also SXI2 (300179) for a locus that maps to chromosome Xq25-q26.
Pegoraro et al. (1997) reported a family ascertained for molecular diagnosis of muscular dystrophy in a young girl, in which preferential activation (greater than 95% of cells) of the paternal X chromosome was seen in both the proband ... Pegoraro et al. (1997) reported a family ascertained for molecular diagnosis of muscular dystrophy in a young girl, in which preferential activation (greater than 95% of cells) of the paternal X chromosome was seen in both the proband and her mother. To determine the molecular basis for skewed X inactivation, they studied X-inactivation patterns in peripheral blood and/or oral mucosal cells from 50 members of the family and from a cohort of normal females. In all females, they found excellent concordance between X-inactivation patterns in blood and oral mucosal cell nuclei. Of the 50 female pedigree members studied, 16 showed preferential use (greater than 95% of cells) of the paternal X chromosome; none of 62 randomly selected females showed similarly skewed X inactivation (p less than 0.0003). The trait for skewed X inactivation was maternally inherited in this family. Naumova et al. (1996) had reported a family with familial skewed X inactivation with preferential use of the paternal X chromosome. This family was of insufficient size, however, to permit genetic mapping of the trait or to establish the pattern of inheritance. Parolini et al. (1998) reported X-linked Wiskott-Aldrich syndrome (WAS; 301000) in an 8-year-old girl. She had a sporadic mutation in the WAS gene (300392), glu133 to lys, on the paternally derived X chromosome, but had nonrandom X inactivation of the maternal X chromosome in both blood and buccal mucosa. Her mother and maternal grandmother also had nonrandom X inactivation, which suggested to the authors the possibility of a defect in XIST (314670) or some other gene involved in the X-inactivation process. Puck and Willard (1998) commented on the subject of X inactivation in females with X-linked disease in reference to the paper by Parolini et al. (1998).
Plenge et al. (1997) identified a mutation in the promoter region of the XIST gene (314670.0001) in multiple females in a family reported by Rupert et al. (1995) as showing nonrandom X-chromosome inactivation.