Patterns of X-linked inheritance: a new approach for the genome era.

Abstract

The concepts of X-linked (XL) "dominant" and "recessive" inheritance originated long before dosage compensation for X chromosome genes was understood, but now have no scientific basis. To address continuing misunderstanding of XL inheritance in humans we reviewed data on penetrance, expressivity, and X chromosome inactivation for 55 XL genes and 57 XL disorders. Our analysis demonstrated widely varying penetrance in heterozygous females and variations in the patterns of inheritance based on the degree of cell selection, severity of the phenotype in males, cell autonomous or non-cell autonomous function of the gene product, and other factors. We propose four new groups of XL disorders with variations in the pattern of inheritance and recommend that the biologically flawed concepts of XL "dominant" and "recessive" inheritance for humans and other therian mammals be retired.