Random X inactivation in a girl with a balanced t(X;9) and an abnormal phenotype

X inactivation is the process by which mammalian females achieve dosage compensation by transcriptionally silencing one X chromosome. In chromosomally normal females, this process is random. However, most females with one abnormal X chromosome demonstrate complete skewing of X inactivation, presumably as the result of cell selection. We present a mentally retarded girl with a 46,X,t(X;9)(q28;q12) karyotype. Analysis of this patient's lymphocytes, using late replication banding and methylation assays for the androgen receptor (AR) and fragile X mental retardation (FMR1) genes, did not show the predicted nonrandom X inactivation pattern. Thus, this patient is functionally disomic for Xq28-qter in a proportion of her cells, most likely resulting in her abnormal phenotype. This case demonstrates the utility of correlating X inactivation patterns with phenotype in females with one structurally abnormal X chromosome, and suggests that both cytogenetic and molecular X inactivation studies should be included in the routine study of these individuals.