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.
Wolff
D J
DJ
Department of Genetics, Case Western Reserve University and Center for Human Genetics, University Hospitals of Cleveland, Ohio, USA.
Schwartz
S
S
Montgomery
T
T
Zackowski
J L
JL
D002648:Child; D002871:Chromosome Banding; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D014178:Translocation, Genetic / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*