Molecular cytogenetic analysis of a duplication Xp in a female with an abnormal phenotype and random X inactivation

We describe a female infant with severe abnormal phenotype with a de novo partial duplication of the short arm of the X chromosome. Chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) was performed with YAC probes, further delineating the breakpoints. The karyotype was 46, X dup(X)(p11-p21.2). Cytogenetic replication studies showed that the normal and duplicated X chromosomes were randomly inactivated in lymphocytes. In most females with structurally abnormal X chromosomes, the abnormal chromosome is inactivated and they are phenotypically apparently normal relatives of phenotypically abnormal males having dupX. Therefore, in this case, there is functional disomy of Xp11-p21.2 in the cells with an active dup(X), most likely resulting in abnormal clinical findings in the patient.