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 nov el human syndrome (''XYXq syndrome'') in which we have detected partia l X disomy, demonstrated supernormal gene expressing resulting from th e absence of X inactivation, and correlated this overexpression with i ts phenotypic consequences. Studies of three unrelated boys with 46,XY q-karyotypes and anomalous phenotypes (severe mental retardation, gene ralized hypotonia and microcephaly) show the presence of a small porti on of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenas e, a representative Xq28 gene product. In all threee cases, the presen ce of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq- Yq interchange occurring in the father's germline.