{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:21:57Z","timestamp":1792167717439,"version":"4.4.0"},"reference-count":34,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:p>Cytogenetic analysis, fluorescent in situ hybridisation (FISH), and molecular amplification have been used to characterise the transfer of Yp fragments to Xp22.3 in six XX males. PCR amplification of the genes SRY, RPS4Y, ZFY, AMELY, KALY, and DAZ and of several other markers along the Y chromosome short and long arms indicated the presence of two different breakpoints in the Y fragment. However, the clinical features were very similar in five of the cases, showing a male phenotype with small testes, testicular atrophy, and azoospermia. All these patients have normal intelligence and a stature within the normal male range. In the remaining case, the diagnosis was made prenatally in a fetus with male genitalia detected by ultrasound and a 46,XX karyotype in amniocytes and fetal blood. Molecular analysis of fetal DNA showed the presence of the SRY gene. FISH techniques also showed Y chromosomal DNA on Xp22.3 in metaphases of placental cells. To our knowledge, this is the second molecular prenatal diagnosis reported of an XX male.<\/jats:p>","DOI":"10.1136\/jmg.35.9.727","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"727-730","source":"Crossref","is-referenced-by-count":32,"title":["Molecular, cytogenetic, and clinical characterisation of six XX males including one prenatal diagnosis."],"prefix":"10.1136","volume":"35","author":[{"given":"E","family":"Margarit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Soler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Carri\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Vendrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Rosell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Ballesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/346240a0","article-title":"A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif","volume":"346","author":"Sinclair, A.H.; Berta, P.; Palmer, M.S.","year":"1990","unstructured":"Sinclair AH, Berta P, Palmer MS, et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 1990;346:240-4.","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/348448a0","article-title":"Genetic evidence equating SRY and the testis-determining factor","volume":"348","author":"Berta, P.; Hawkins, JR, Sinclair; A.H.","year":"1990","unstructured":"Berta P, Hawkins JR, Sinclair AH, et al. Genetic evidence equating SRY and the testis-determining factor. Nature 1990;348:448-50.","journal-title":"Nature"},{"key":"ref_3","first-page":"117","article-title":"Male development of chromosomally female mice transgenic for Sry","volume":"351","author":"Koopman, P.; Gubbay, J.; Vivian, N.; Goodfellow, P.; LovellBadge, R.","year":"1990","unstructured":"Koopman P, Gubbay J, Vivian N, Goodfellow P, LovellBadge R. Male development of chromosomally female mice transgenic for Sry. Nature 1990;351:117-21.","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF00284157","article-title":"The etiology of maleness in XX men","volume":"58","author":"la Chapelle A, De","year":"1981","unstructured":"De la Chapelle A. The etiology of maleness in XX men. Hum Genet 1981;58:105-16.","journal-title":"Hum Genet"},{"key":"ref_5","first-page":"25","article-title":"XX sex chromosomes in a human male","volume":"412","author":"la Chapelle A, De; H, Hortling; M, Niemi; J, Wennstrom","year":"1964","unstructured":"De la Chapelle A, Hortling H, Niemi M, Wennstrom J. XX sex chromosomes in a human male. First case. Acta Med Scand 1964;412:25-38.","journal-title":"First case. Acta Med Scand"},{"key":"ref_6","first-page":"1723","article-title":"Human XX males with Y single copy DNA fragments","volume":"307","author":"Guellaen, G.; Casanova, M.; Bishop, C.","year":"1984","unstructured":"Guellaen G, Casanova M, Bishop C, et al. Human XX males with Y single copy DNA fragments. Nature 1984;307:1723.","journal-title":"Nature"},{"key":"ref_7","first-page":"7325","article-title":"Variable transfer of Y-specific sequences in XX males","volume":"15","author":"Affara, N.A.; Ferguson-Smith, M.; Tolmie, J.","year":"1986","unstructured":"Affara NA, Ferguson-Smith M, Tolmie J, et al. Variable transfer of Y-specific sequences in XX males. Nucleic Acids Res 1986;15:7325-42.","journal-title":"Nucleic Acids Res"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/328437a0","article-title":"Y-chromosomal short arms in human XX males","volume":"328","author":"Page, D.C.; Brown, L.G.; de la Chapelle A. Exchange of terminal portions of X-and","year":"1987","unstructured":"Page DC, Brown LG, de la Chapelle A. Exchange of terminal portions of X-and Y-chromosomal short arms in human XX males. Nature 1987;328:437-40.","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF00207036","article-title":"Molecular cytogenetic analysis of XX males using Y-specific DNA sequences, including SRY","volume":"89","author":"de Auwera R, Van; N, Van Roy; A, De Paepe","year":"1992","unstructured":"Van de Auwera R, Van Roy N, De Paepe A, et al. Molecular cytogenetic analysis of XX males using Y-specific DNA sequences, including SRY. Hum Genet 1992;89:23-8.","journal-title":"Hum Genet"},{"key":"ref_10","first-page":"623","article-title":"Development in a 46, XX boy with positive SRY gene","volume":"9","author":"Rego, A.; Margarit, E.; Estivill, X.; Regal, M.; Garcia-Mayor, R.V.","year":"1996","unstructured":"Rego A, Margarit E, Estivill X, Regal M, Garcia-Mayor RV. Development in a 46,XX boy with positive SRY gene. J Pediatr Endocrinol Metab 1996;9:623-6.","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0140-6736(66)92778-4","article-title":"X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome","volume":"ii:","author":"Ferguson-Smith, M.A.","year":"1966","unstructured":"Ferguson-Smith MA. X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome. Lancet 1966;ii:475-6.","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00291496","article-title":"Chromosome measurements on an XXp+ male","volume":"32","author":"Madan, K.","year":"1976","unstructured":"Madan K. Chromosome measurements on an XXp+ male. Hum Genet 1976;32:141-2.","journal-title":"Hum Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00277683","article-title":"Heteromorphic X chromosomes in 46, XX males: evidence for the involvement of X-Y interchange","volume":"49","author":"Evans, H.J.; Buckton, K.E.; Spowart, G.; Carothers, A.D.","year":"1979","unstructured":"Evans HJ, Buckton KE, Spowart G, Carothers AD. Heteromorphic X chromosomes in 46,XX males: evidence for the involvement of X-Y interchange. Hum Genet 1979;49:11-31.","journal-title":"Hum Genet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.3738510","article-title":"Chromosome Y-specific DNA is transferred to the short arm of X chromosome in human XX males","volume":"233","author":"Andersson, M.; Page, D.C.; de la Chapelle, A.","year":"1986","unstructured":"Andersson M, Page DC, de la Chapelle A. Chromosome Y-specific DNA is transferred to the short arm of X chromosome in human XX males. Science 1986;233:786-8.","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/BF00281064","article-title":"Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe","volume":"75","author":"Magenis, R.E.; Casanova, M.; Fellous, M.; Olson, S.; Sheehy, R.","year":"1987","unstructured":"Magenis RE, Casanova M, Fellous M, Olson S, Sheehy R. Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe. Hum Genet 1987;75:228-33.","journal-title":"Hum Genet"},{"key":"ref_16","first-page":"145","article-title":"Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics","volume":"85","author":"Jaunch, A.; Daumer, C.; Lichter, P.; Schroeder-Kurth, T.; Cremer, T.","year":"1990","unstructured":"Jaunch A, Daumer C, Lichter P, Schroeder-Kurth T, Cremer T. Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics. Hum Genet 1990;85:145-50.","journal-title":"Hum Genet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/315224a0","article-title":"Chromosome Y-specific DNA in related human XX males","volume":"315","author":"Page, D.C.; de la Chapelle, A.; Weissenbach, J.","year":"1985","unstructured":"Page DC, de la Chapelle A, Weissenbach J. Chromosome Y-specific DNA in related human XX males. Nature 1985; 315:224-6.","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/BF00272440","article-title":"Absence of Y-specific DNA sequences in human 46, XX true hermaphrodites and in 45, X mixed gonadal dysgenesis","volume":"76","author":"Waibel, F.; Scherer, G.; Fraccaro, M.","year":"1987","unstructured":"Waibel F, Scherer G, Fraccaro M, et al. Absence of Y-specific DNA sequences in human 46,XX true hermaphrodites and in 45,X mixed gonadal dysgenesis. Hum Genet 1987;76:332-6.","journal-title":"Hum Genet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/BF00293890","article-title":"Localization of Y chromosome sequences and X chromosomal replication studies in XX males","volume":"81","author":"Schempp, W.; Muller, G.; Scherer, G.","year":"1989","unstructured":"Schempp W, Muller G, Scherer G, et al. Localization of Y chromosome sequences and X chromosomal replication studies in XX males. Hum Genet 1989;81:144-8.","journal-title":"Hum Genet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/ajmg.1320410127","article-title":"PCR detection of distal Yp sequences in an XX true hermaphrodite","volume":"41","author":"Nakagome, Y.; Seki, S.; Fukutani, K.; Nagafuchi, S.; Nakahori, Y.; Tamura, T.","year":"1991","unstructured":"Nakagome Y, Seki S, Fukutani K, Nagafuchi S, Nakahori Y, Tamura T. PCR detection of distal Yp sequences in an XX true hermaphrodite. Am J Med Genet 1991;41:112-14.","journal-title":"Am J Med Genet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1126\/science.1439769","article-title":"The human Y chromosome: a 43-interval map based on naturally occurring deletions","volume":"258","author":"Vollrath, D.; Foote, S.; Hilton, A.","year":"1992","unstructured":"Vollrath D, Foote S, Hilton A, et al. The human Y chromosome: a 43-interval map based on naturally occurring deletions. Science 1992;258:52-9.","journal-title":"Science"},{"key":"ref_22","first-page":"356","article-title":"A possible common mechanism of \"Y-negative\" human XX males and XX true hermaphrodites","volume":"84","author":"Abbas, N.E.; Toublanc, J.E.; Boucekkine, C.","year":"1990","unstructured":"Abbas NE, Toublanc JE, Boucekkine C, et al. A possible common mechanism of \"Y-negative\" human XX males and XX true hermaphrodites. Hum Genet 1990;84:356-60.","journal-title":"Hum Genet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000185438","article-title":"Report of an XX male with hypospadias and pubertal gynecomastia, SRY gene negative in blood leukocytes but SRY gene positive in testicular cells","volume":"47","author":"Dardis, A.; Saraco, N.; Mendilaharzu, H.; Rivarola, M.; Belgorosky, A.","year":"1997","unstructured":"Dardis A, Saraco N, Mendilaharzu H, Rivarola M, Belgorosky A. Report of an XX male with hypospadias and pubertal gynecomastia, SRY gene negative in blood leukocytes but SRY gene positive in testicular cells. Horm Res 1997;47:85-8.","journal-title":"Horm Res"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/344663a0","article-title":"Population structure of the human pseudoautosomal boundary","volume":"344","author":"Ellis, N.; Taylor, A.; Bengtsson, B.O.; Kidd, J.; Rogers, J.; Goodfellow, P.","year":"1990","unstructured":"Ellis N, Taylor A, Bengtsson BO, Kidd J, Rogers J, Goodfellow P. Population structure of the human pseudoautosomal boundary. Nature 1990;344:663-5.","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/ng0794-414","article-title":"Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness","volume":"7","author":"Weil, D.; Wang, I.; Dietrich, A.; Poustka, A.; Weissenbach, J.; Petit, C.","year":"1994","unstructured":"Weil D, Wang I, Dietrich A, Poustka A, Weissenbach J, Petit C. Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness. Nat Genet 1994;7:414-19.","journal-title":"Nat Genet"},{"key":"ref_26","first-page":"90","volume":"128","author":"F, Lo Curto; E, Pucci; S, Scappaticci","year":"1974","unstructured":"Lo Curto F, Pucci E, Scappaticci S, et al. XO and male phenotype. Am _Dis Child 1974;128:90-1.","journal-title":"XO and male phenotype. Am _Dis Child"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1399-0004.1977.tb00908.x","article-title":"Male with 45, X karyotype","volume":"12","author":"Forabosco, A.; Carratu, A.; Assuma, M.; De Pol, A.; Dutrillaux, B.; Cheli, E.","year":"1977","unstructured":"Forabosco A, Carratu A, Assuma M, De Pol A, Dutrillaux B, Cheli E. Male with 45,X karyotype. Clin Genet 1977;12: 97-100.","journal-title":"Clin Genet"},{"key":"ref_28","first-page":"477","article-title":"A 45, X male with Y-specific DNA translocated onto chromosome","volume":"40","author":"Gal, A.; Weber, B.; Neri, G.","year":"1987","unstructured":"Gal A, Weber B, Neri G, et al. A 45,X male with Y-specific DNA translocated onto chromosome 15. Am 7 Hum Genet 1987;40:477-88.","journal-title":"15. Am 7 Hum Genet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/BF01790089","article-title":"Molecular detection of a Y\/1 8 translocation in a 45, X holoprosencephalic male","volume":"80","author":"Munke, M.; Page, D.C.; Brown, L.G.","year":"1988","unstructured":"Munke M, Page DC, Brown LG, et al. Molecular detection of a Y\/1 8 translocation in a 45,X holoprosencephalic male. Hum Genet 1988;80:219-23.","journal-title":"Hum Genet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1098\/rstb.1988.0121","article-title":"Accidental X-Y recombination and the aetiology of XX males and true hermaphrodites","volume":"322","author":"Ferguson-Smith, M.A.; Affara, N.A.","year":"1988","unstructured":"Ferguson-Smith MA, Affara NA. Accidental X-Y recombination and the aetiology of XX males and true hermaphrodites. Philos Trans R Soc Lond (Biol) 1988;322:133.","journal-title":"Philos Trans R Soc Lond (Biol)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0140-6736(94)91029-4","article-title":"SRY-negative XX fetus with complete male genitalia","volume":"343","author":"Vilain, E.; Le Fiblec, B.; Morichon-Dellvallez, N.","year":"1994","unstructured":"Vilain E, Le Fiblec B, Morichon-Dellvallez N, et al. SRY-negative XX fetus with complete male genitalia. Lancet 1994;343:240-1.","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/0140-6736(92)90245-X","article-title":"Prenatal cytogenetic and postnatal molecular studies on 46, XX male","volume":"339","author":"Sachs, E.S.; Van Hemel, J.O.; Los, F.J.","year":"1992","unstructured":"Sachs ES, Van Hemel JO, Los FJ. Prenatal cytogenetic and postnatal molecular studies on 46,XX male. Lancet 1992;339: 180-1.","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/ng0895-383","article-title":"Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene","volume":"10","author":"Reijo, R.; Lee, T.Y.; Salo, P.","year":"1995","unstructured":"Reijo R, Lee TY, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 1995;10: 383-93.","journal-title":"Nat Genet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S0140-6736(96)90938-1","article-title":"Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome","volume":"347","author":"Reijo, R.; Alagappan, R.K.; Patrizio, P.; Page, D.C.","year":"1996","unstructured":"Reijo R, Alagappan RK, Patrizio P, Page DC. Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. 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