title: X-inactivation and human disease: X-linked dominant male-lethal disorders.
abstract: X chromosome inactivation (XCI) is the process by which the dosage imbalance of X-linked genes between XX females and XY males is functionally equalized. XCI modulates the phenotype of females carrying mutations in X-linked genes, as observed in X-linked dominant male-lethal disorders such as oral-facial-digital type I (OFDI) and microphthalmia with linear skin-defects syndromes. The remarkable degree of heterogeneity in the XCI pattern among female individuals, as revealed by the recently reported XCI profile of the human X chromosome, could account for the phenotypic variability observed in these diseases. Furthermore, the recent characterization of a murine model for OFDI shows how interspecies differences in the XCI pattern between Homo sapiens and Mus musculus result in discrepancies between the phenotypes observed in patients and mice.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131, Naples, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D000818:Animals; D004194:Disease; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D005804:Genes, Lethal / Q000235:genetics*; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*