Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders

Abstract

Some deleterious X-linked mutations may result in a growth disadvantage for those cells in which the mutation, when on the active X chromosome, affects cell proliferation or viability. To explore the relationship between skewed X-chromosome inactivation and X-linked mental retardation (XLMR) disorders, we used the androgen receptor X-inactivation assay to determine X-inactivation patterns in 155 female subjects from 24 families segregating 20 distinct XLMR disorders. Among XLMR carriers, ∼50% demonstrate markedly skewed X inactivation (i.e., patterns ≥80:20), compared with only ∼10% of female control subjects (P