Serologic Detection of a Y-Linked Gene in XX Males and XX True Hermaphrodites

To test the hypothesis that H-Y antigen (present on both somatic and germ cells in normal males but not normal females) is essential for testicular differentiation, we studied four XX males and three XX true hermaphrodites. Blood cells from six subjects and cultured gonadal fibroblasts from a seventh expressed H-Y antigen. Since expression of this antigen requires the presence of a gene normally carried by the Y chromosome, this gene, and perhaps additional Y chromosomal material, should have been present in the genome of these subjects. In one patient this presence is accounted for by a Y-to-X translocation, detectable by chromosome banding. In another a normal Y chromosome was present in a minor population of cells. In the remaining five, no karyotypic abnormality was detectable. Immunologic detection of H-Y antigen is a sensitive test for the presence of the Y chromosome or of its male-determining segment. (N Engl J Med 295:750–754, 1976) Studies of abnormal sex-chromosome constitutions in human beings, mice and other animals have established the importance of the Y chromosome in mammalian sex determination. Thus, mammalian testicular differentiation occurs only when all or part of the Y chromosome is present in at least some embryonic cells.¹ For many years the only apparent exception to this rule has been masculinization of the embryonic gonads in XX true hermaphrodites and XX males with Klinefelter syndrome, both of which lack a recognizable Y chromosome.² The occasional occurrence of true hermaphroditism or Klinefelter syndrome in XX/XXY mosaics^3,4 and of true hermaphroditism in XX/XY chimeras.