MILD PHENOTYPIC EFFECTS OF A DE-NOVO DELETION-XPTER-]XP22.3 AND DUPLICATION-3PTER-]3P23

We report on a girl with a de novo monosomy Xpter --> Xp22.3 and triso my 3pter --> 3p23, normal development and stature, mildly affected phe notype, and learning disabilities with a low normal level of intellige nce, Late replication studies using BudR demonstrated that the entire der(X) was inactive in 30% of cells, In 62% of cells the inactivation did not spread to the autosomal segment in the der(X). The normal X wa s inactivated in 8% of cells. Quantitative X-inactivation studies usin g the human androgen receptor locus assay (HAR) on peripheral leukocyt es and buccal epithelial cells showed extreme skewing of methylation ( 90.4% of the paternal allele), The correlation of cytogenetic and mole cular data suggest that the mild phenotype of the proposita is most li kely due to preferential inactivation of the entire der(X), which seem s to be of paternal origin. (C) 1995 Wiley-Liss, Inc.