XQ-YQ INTERCHANGE RESULTING IN SUPERNORMAL X-LINKED GENE-EXPRESSION IN SEVERELY RETARDED MALES WITH 46,XYQ-KARYOTYPE

The critical importance of dosage compensation is underscored by a novel human syndrome (''XYXq syndrome'') in which we have detected partial X disomy, demonstrated supernormal gene expressing resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq-karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all threee cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline.