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 expression 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 three cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline.
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Howard Hughes Research Laboratories at Whitehead Institute, Cambridge, Massachusetts 02142.
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D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D003434:Crossing Over, Genetic; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D009123:Muscle Hypotonia / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012640:Seizures / Q000235:genetics; D013091:Spermatogenesis; D014960:X Chromosome; D014998:Y Chromosome / Q000648:ultrastructure*
D005954:Glucosephosphate Dehydrogenase