{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:33:16Z","timestamp":1784687596124,"version":"3.55.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2009,6,10]],"date-time":"2009-06-10T00:00:00Z","timestamp":1244592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2009,12]]},"DOI":"10.1038\/ejhg.2009.96","type":"journal-article","created":{"date-parts":[[2009,6,10]],"date-time":"2009-06-10T10:21:50Z","timestamp":1244629310000},"page":"1642-1649","source":"Crossref","is-referenced-by-count":31,"title":["A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma"],"prefix":"10.1038","volume":"17","author":[{"given":"Remko","family":"Hersmus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertie HCGM","family":"de Leeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Stoop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena C","family":"van Doorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hennie T","family":"Br\u00fcggenwirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stenvert LS","family":"Drop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Wolter","family":"Oosterhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent R","family":"Harley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leendert HJ","family":"Looijenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,6,10]]},"reference":[{"key":"BFejhg200996_CR1","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1136\/adc.2006.098319","volume":"91","author":"IA Hughes","year":"2006","unstructured":"Hughes IA, Houk C, Ahmed SF, Lee PA, Group LC, Group EC : Consensus statement on management of intersex disorders. Arch Dis Child 2006; 91: 554\u2013563.","journal-title":"Arch Dis Child"},{"key":"BFejhg200996_CR2","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1210\/er.2006-0005","volume":"27","author":"M Cools","year":"2006","unstructured":"Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH : Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev 2006; 27: 468\u2013484.","journal-title":"Endocr Rev"},{"key":"BFejhg200996_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.ydbio.2004.07.011","volume":"274","author":"R Sekido","year":"2004","unstructured":"Sekido R, Bar I, Narvaez V, Penny G, Lovell-Badge R : SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors. Dev Biol 2004; 274: 271\u2013279.","journal-title":"Dev Biol"},{"key":"BFejhg200996_CR4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.ydbio.2005.08.039","volume":"287","author":"D Wilhelm","year":"2005","unstructured":"Wilhelm D, Martinson F, Bradford S et al: Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Dev Biol 2005; 287: 111\u2013124.","journal-title":"Dev Biol"},{"key":"BFejhg200996_CR5","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/nature06944","volume":"453","author":"R Sekido","year":"2008","unstructured":"Sekido R, Lovell-Badge R : Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 2008; 453: 930\u2013934.","journal-title":"Nature"},{"key":"BFejhg200996_CR6","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nrg1903","volume":"7","author":"D Wilhelm","year":"2006","unstructured":"Wilhelm D, Koopman P : The makings of maleness: towards an integrated view of male sexual development. Nat Rev Genet 2006; 7: 620\u2013631.","journal-title":"Nat Rev Genet"},{"key":"BFejhg200996_CR7","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/nar\/22.8.1500","volume":"22","author":"VR Harley","year":"1994","unstructured":"Harley VR, Lovell-Badge R, Goodfellow PN : Definition of a consensus DNA binding site for SRY. Nucleic Acids Res 1994; 22: 1500\u20131501.","journal-title":"Nucleic Acids Res"},{"key":"BFejhg200996_CR8","doi-asserted-by":"publisher","first-page":"3368","DOI":"10.1073\/pnas.91.8.3368","volume":"91","author":"K Giese","year":"1994","unstructured":"Giese K, Pagel J, Grosschedl R : Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors. Proc Natl Acad Sci USA 1994; 91: 3368\u20133372.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFejhg200996_CR9","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1002\/1097-0142(197006)25:6<1340::AID-CNCR2820250612>3.0.CO;2-N","volume":"25","author":"RE Scully","year":"1970","unstructured":"Scully RE : Gonadoblastoma\/ a review of 74 cases. Cancer 1970; 25: 1340\u20131356.","journal-title":"Cancer"},{"key":"BFejhg200996_CR10","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nrc1568","volume":"5","author":"JW Oosterhuis","year":"2005","unstructured":"Oosterhuis JW, Looijenga LH : Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 2005; 5: 210\u2013222.","journal-title":"Nat Rev Cancer"},{"key":"BFejhg200996_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/path.2335","volume":"215","author":"R Hersmus","year":"2008","unstructured":"Hersmus R, Kalfa N, de Leeuw B et al: FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). J Pathol 2008; 215: 31\u201338.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR12","doi-asserted-by":"crossref","unstructured":"Almstrup K, Ottesen AM, Sonne SB et al: Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ. Cell Tissue Res 2005.","DOI":"10.1007\/s00441-005-1084-x"},{"key":"BFejhg200996_CR13","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1002\/path.1587","volume":"203","author":"F Honecker","year":"2004","unstructured":"Honecker F, Stoop H, de Krijger RR, Chris Lau YF, Bokemeyer C, Looijenga LH : Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells. J Pathol 2004; 203: 849\u2013857.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR14","first-page":"2244","volume":"63","author":"LH Looijenga","year":"2003","unstructured":"Looijenga LH, Stoop H, de Leeuw HP et al: POU5F1 (OCT3\/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res 2003; 63: 2244\u20132250.","journal-title":"Cancer Res"},{"key":"BFejhg200996_CR15","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/path.1766","volume":"206","author":"J de Jong","year":"2005","unstructured":"de Jong J, Stoop H, Dohle GR et al: Diagnostic value of OCT3\/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol 2005; 206: 242\u2013249.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/path.2105","volume":"211","author":"L Cheng","year":"2007","unstructured":"Cheng L, Sung MT, Cossu-Rocca P et al: OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol 2007; 211: 1\u20139.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR17","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.1210\/jc.2005-0139","volume":"90","author":"M Cools","year":"2005","unstructured":"Cools M, van Aerde K, Kersemaekers AM et al: Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes. J Clin Endocrinol Metab 2005; 90: 5295\u20135303.","journal-title":"J Clin Endocrinol Metab"},{"key":"BFejhg200996_CR18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/path.2378","volume":"216","author":"H Stoop","year":"2008","unstructured":"Stoop H, Honecker F, van de Geijn GJ et al: Stem cell factor as a novel diagnostic marker for early malignant germ cells. J Pathol 2008; 216: 43\u201354.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1242\/dev.101.Supplement.151","volume":"101","author":"DC Page","year":"1987","unstructured":"Page DC : Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development 1987; 101: 151\u2013155.","journal-title":"Development"},{"key":"BFejhg200996_CR20","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1093\/hmg\/5.11.1801","volume":"5","author":"F Schnieders","year":"1996","unstructured":"Schnieders F, Dork T, Arnemann J, Vogel T, Werner M, Schmidtke J : Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum Mol Genet 1996; 5: 1801\u20131807.","journal-title":"Hum Mol Genet"},{"key":"BFejhg200996_CR21","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1159\/000056838","volume":"91","author":"Y Lau","year":"2000","unstructured":"Lau Y, Chou P, Iezzoni J, Alonzo J, Komuves L : Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma. Cytogenet Cell Genet 2000; 91: 160\u2013164.","journal-title":"Cytogenet Cell Genet"},{"key":"BFejhg200996_CR22","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1093\/humrep\/deh800","volume":"20","author":"H Stoop","year":"2005","unstructured":"Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, Looijenga LH : Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Hum Reprod 2005; 20: 1466\u20131476.","journal-title":"Hum Reprod"},{"key":"BFejhg200996_CR23","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/gene.20147","volume":"42","author":"T Kido","year":"2005","unstructured":"Kido T, Lau YF : A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons. Genesis 2005; 42: 263\u2013275.","journal-title":"Genesis"},{"key":"BFejhg200996_CR24","doi-asserted-by":"publisher","first-page":"7045","DOI":"10.1073\/pnas.1137864100","volume":"100","author":"VR Harley","year":"2003","unstructured":"Harley VR, Layfield S, Mitchell CL et al: Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proc Natl Acad Sci USA 2003; 100: 7045\u20137050.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFejhg200996_CR25","doi-asserted-by":"publisher","first-page":"33839","DOI":"10.1074\/jbc.M302078200","volume":"278","author":"A Argentaro","year":"2003","unstructured":"Argentaro A, Sim H, Kelly S et al: A SOX9 defect of calmodulin-dependent nuclear import in campomelic dysplasia\/autosomal sex reversal. J Biol Chem 2003; 278: 33839\u201333847.","journal-title":"J Biol Chem"},{"key":"BFejhg200996_CR26","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/path.1766","volume":"206","author":"J De Jong","year":"2005","unstructured":"De Jong J, Stoop J, Dohle GR et al: Diagnostic value of OCT3\/4 for pre-invasive and invasive testicular germ cell tumors. J Pathol 2005; 206: 242\u2013249.","journal-title":"J Pathol"},{"key":"BFejhg200996_CR27","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/sj.embor.7400279","volume":"5","author":"J Kehler","year":"2004","unstructured":"Kehler J, Tolkunova E, Koschorz B et al: Oct4 is required for primordial germ cell survival. EMBO Rep 2004; 5: 1078\u20131083.","journal-title":"EMBO Rep"},{"key":"BFejhg200996_CR28","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.humpath.2005.02.016","volume":"36","author":"AM Kersemaekers","year":"2005","unstructured":"Kersemaekers AM, Honecker F, Stoop H et al: Identification of germ cells at risk for neoplastic transformation in gonadoblastoma: an immunohistochemical study for OCT3\/4 and TSPY. Hum Pathol 2005; 36: 512\u2013521.","journal-title":"Hum Pathol"},{"key":"BFejhg200996_CR29","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1086\/302353","volume":"64","author":"YF Lau","year":"1999","unstructured":"Lau YF : Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet 1999; 64: 921\u2013927.","journal-title":"Am J Hum Genet"},{"key":"BFejhg200996_CR30","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/1471-2407-6-154","volume":"6","author":"SW Oram","year":"2006","unstructured":"Oram SW, Liu XX, Lee TL, Chan WY, Lau YF : TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells. BMC Cancer 2006; 6: 154.","journal-title":"BMC Cancer"},{"key":"BFejhg200996_CR31","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1016\/j.humpath.2007.03.011","volume":"38","author":"Y Li","year":"2007","unstructured":"Li Y, Tabatabai ZL, Lee TL et al: The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors. Hum Pathol 2007; 38: 1470\u20131481.","journal-title":"Hum Pathol"},{"key":"BFejhg200996_CR32","doi-asserted-by":"publisher","first-page":"5858","DOI":"10.1038\/sj.onc.1203950","volume":"19","author":"C Rosenberg","year":"2000","unstructured":"Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW, Looijenga LH : Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas. Oncogene 2000; 19: 5858\u20135862.","journal-title":"Oncogene"},{"key":"BFejhg200996_CR33","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1054\/bjoc.2001.1889","volume":"85","author":"B Summersgill","year":"2001","unstructured":"Summersgill B, Osin P, Lu YJ, Huddart R, Shipley J : Chromosomal imbalances associated with carcinoma in situ and associated testicular germ cell tumours of adolescents and adults. Br J Cancer 2001; 85: 213\u2013220.","journal-title":"Br J Cancer"},{"key":"BFejhg200996_CR34","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/372525a0","volume":"372","author":"JW Foster","year":"1994","unstructured":"Foster JW, Dominguez-Steglich MA, Guioli S et al: Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 1994; 372: 525\u2013530.","journal-title":"Nature"},{"key":"BFejhg200996_CR35","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/ng0996-62","volume":"14","author":"S Morais da Silva","year":"1996","unstructured":"Morais da Silva S, Hacker A, Harley V, Goodfellow P, Swain A, Lovell-Badge R : Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nat Genet 1996; 14: 62\u201368.","journal-title":"Nat Genet"},{"key":"BFejhg200996_CR36","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1242\/dev.00969","volume":"131","author":"D Schmidt","year":"2004","unstructured":"Schmidt D, Ovitt CE, Anlag K et al: The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 2004; 131: 933\u2013942.","journal-title":"Development"},{"key":"BFejhg200996_CR37","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1093\/hmg\/ddh124","volume":"13","author":"M Uda","year":"2004","unstructured":"Uda M, Ottolenghi C, Crisponi L et al: Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum Mol Genet 2004; 13: 1171\u20131181.","journal-title":"Hum Mol Genet"},{"key":"BFejhg200996_CR38","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1095\/biolreprod.105.045930","volume":"74","author":"F Barrionuevo","year":"2006","unstructured":"Barrionuevo F, Bagheri-Fam S, Klattig J et al: Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biol Reprod 2006; 74: 195\u2013201.","journal-title":"Biol Reprod"},{"key":"BFejhg200996_CR39","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1006\/dbio.2001.0438","volume":"240","author":"KH Albrecht","year":"2001","unstructured":"Albrecht KH, Eicher EM : Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor. Dev Biol 2001; 240: 92\u2013107.","journal-title":"Dev Biol"},{"key":"BFejhg200996_CR40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/genetics\/164.1.277","volume":"164","author":"KH Albrecht","year":"2003","unstructured":"Albrecht KH, Young M, Washburn LL, Eicher EM : Sry expression level and protein isoform differences play a role in abnormal testis development in C57BL\/6J mice carrying certain Sry alleles. Genetics 2003; 164: 277\u2013288.","journal-title":"Genetics"},{"key":"BFejhg200996_CR41","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/S0169-328X(03)00339-5","volume":"118","author":"P Dewing","year":"2003","unstructured":"Dewing P, Shi T, Horvath S, Vilain E : Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Brain Res Mol Brain Res 2003; 118: 82\u201390.","journal-title":"Brain Res Mol Brain Res"},{"key":"BFejhg200996_CR42","doi-asserted-by":"publisher","first-page":"9005","DOI":"10.1523\/JNEUROSCI.22-20-09005.2002","volume":"22","author":"GJ De Vries","year":"2002","unstructured":"De Vries GJ, Rissman EF, Simerly RB et al: A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J Neurosci 2002; 22: 9005\u20139014.","journal-title":"J Neurosci"},{"key":"BFejhg200996_CR43","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.cub.2006.01.017","volume":"16","author":"P Dewing","year":"2006","unstructured":"Dewing P, Chiang CW, Sinchak K et al: Direct regulation of adult brain function by the male-specific factor SRY. Curr Biol 2006; 16: 415\u2013420.","journal-title":"Curr Biol"}],"container-title":["European Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ejhg200996.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ejhg200996","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ejhg200996.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T16:59:30Z","timestamp":1684429170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ejhg200996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,10]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["BFejhg200996"],"URL":"https:\/\/doi.org\/10.1038\/ejhg.2009.96","relation":{},"ISSN":["1018-4813","1476-5438"],"issn-type":[{"value":"1018-4813","type":"print"},{"value":"1476-5438","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,10]]}}}