Systematic analysis of X-inactivation in 19XLMR families: extremely skewedprofiles in carriers in three families

It has been demonstrated in several X-linked disorders, both with and witho ut mental retardation, that the X-inactivation process plays a significant role in the expression of X-linked diseases in females. Moreover, in some d isorders extremely skewed inactivation of the X chromosome is constant in c arriers, and this is thought to result from a proliferation or a survival a dvantage for cells expressing the normal allele at this locus over cells ex pressing the mutated allele. X-linked mental retardation (XLMR) is heteroge neous, and cloning and characterization of the mutated genes are in progres s. XLMR can be expressed in carrier females but often with milder manifesta tions. We report the systematic study of the X-inactivation profile of obli gate carriers and other females in 19 multiplex XLMR pedigrees, using leuco cyte-extracted DNA. Extremely skewed profiles were observed in carriers in three of 19 families.