PARTIAL X-CHROMOSOME TRISOMY WITH FUNCTIONAL DISOMY OF XP DUE TO FAILURE OF X-INACTIVATION

A 5-month-old girl with mild phenotypic abnormalities, developmental d elay, and seizures was found to have the de novo karyotype 46XX, - 13, + der(13)t(X;13)(p21.2;p11.1). The partial trisomy of Xp21.2 --> pter was confirmed with fluorescence in situ hybridization, using an X chr omosome painting probe and several cosmid and YAC probes for Xp sequen ces. Replication banding showed that one of the structurally normal X chromosomes was late-replicating, but that the Xp segment of the der(1 3) was early-replicating in all cells examined. Since segments of the X chromosome separated from the X inactivation center in Xq13.2 cannot undergo X inactivation, the result is functional disomy of distal Xp. As the loss of short arm material from chromosome 13 is not considere d to be clinically significant, the genomic imbalance of Xp expressed in this patient most likely accounts for her abnormal phenotype. (C) 1 994 Wiley-Liss,Inc.