X inactivation patterns in two syndromes with probable X-linked dominant, male lethal inheritance.
For Incontinentia pigmenti Bloch-Sulzberger (IP) and Aicardi syndrome, an X-linked dominant transmission with lethality in hemizygous males has been proposed. The typical transition from inflammation to verrucous hypertrophy and hyperpigmented skin areas in IP suggests a gradual replacement of defective cells by normal cells. This would imply a preferential inactivation of the X chromosome carrying the IP gene with a proliferative advantage of this cell population. We have confirmed this hypothesis by demonstrating that the same X chromosome is preferentially active in fibroblasts grown from normal and hyperpigmented skin of an affected girl. In contrast, X inactivation was random in a girl with Aicardi syndrome.
D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D005799:Genes, Dominant; D005804:Genes, Lethal; D008040:Genetic Linkage; D006801:Humans; D006822:Hybrid Cells / Q000648:ultrastructure; D008297:Male; D051379:Mice; D010859:Pigmentation Disorders / Q000235:genetics*; D012867:Skin / Q000648:ultrastructure; D013577:Syndrome; D014960:X Chromosome