Complete or 'true' hydatidiform mole, an abnormality of human gestation, is characterized by hydropic degeneraton of all placental villi, marked hypertrophy of the trophoblast, absence of a fetus and a propensity to become malignant. The chromosome constitution of complete moles is usually 46,XX, and Kajii et al. reported that the entire genome in seven out of seven cases was paternal in origin, with all centromere markers homozygous for paternal heteromorphisms. These observations, since confirmed, can be explained by the fertilization of an 'empty' egg--no effective genome--by either a haploid sperm that then duplicates without cytokinesis, to restore the diploid number, or by a diploid sperm resulting from failure of the second meiotic division. We report here a study of a series of complete moles that shows the first alternative to be correct in the majority of cases.

We report a unique and complex karyotypic rearrangement involving chromosomes X, 3, 7, and 21. Blood cells and fibroblasts from the proband do not express the maternal allele for glucose-6phosphate dehydrogenase (G6PD), providing biochemical evidence for nonrandom expression of X-linked genes in balanced X-autosome translocations. The break point on the X chromosome, at the junction of Xq27-Xq28, separates the loci for hypoxanthine phosphoribosyltransferase (HPRT) and G6PD. Studies of mouse-human hybrids derived from the roband's cells indicate that G6PD, at q28, is clearly distal to all other X loci now assigned. From these and previous studies, we can localize HPRT to that segment between Xq26 and Xq27. The studies also provide further evidence for the stability of the inactive X phenotype in hybrid cells.Among the loci most important to mammalian geneticists are the X-linked genes for glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8). The availability of spontaneous and induced variants at these loci in humans has contributed to their usefulness for study of basic genetic phenomena, specifically the regulation of X chromosome activity (1). It is likely that these genes will provide the means to obtain and identify Xchromosome-specific DNA. Although it is known that these loci are on the distal region of the long arm of the human X chromosome (2-4), their localization and order with respect to the centromere have not been unequivocally established. Studies of radiation-induced chromosome fragments in somatic cell hybrids suggest that the two loci are separable and that G6PD is distal to HPRT (5), but interpretation of these studies has been questioned (6).Because more precise localization of these loci might facilitate isolation of these X-linked genes, we report studies utilizing X-autosome translocations. Our results indicate that the HPRT locus is between Xq26 and Xq27 and G6PD is more telomeric, being on band Xq28. Furthermore, studies of the human parental cells have provided biochemical evidence for nonrandom expression of X-linked genes in individuals with a balanced X-autosome translocation. MATERIALS AND METHODSSubjects. Skin fibroblast cultures were established from a 17-month-old black female with mental retardation and a complex karyotypic rearrangement (7). Cultures were also established from maternal skin fibroblasts as well as from leukocytes of the proband and both parents.Medium. Cells were maintained in Eagle's minimal essentialThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 2810 medium (GIBCO), enriched as described (8). Selection for hybrids was carried out in HOT medium-that is, hypoxanthine/amethopterin/thymidine (HAT) medium containing 1 ,uM ouabain (8). Medium containing 60 /iM 6-thioguanine (6TG) was used to select for HPRT-deficient cells from the pro...

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