{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:48:13Z","timestamp":1787021293620,"version":"build-2736575974"},"reference-count":40,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X).<\/jats:p>\n                  <jats:p>Patients: A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis.<\/jats:p>\n                  <jats:p>Results: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage.<\/jats:p>\n                  <jats:p>Conclusions: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.<\/jats:p>","DOI":"10.1210\/jc.2007-2155","type":"journal-article","created":{"date-parts":[[2007,11,13]],"date-time":"2007-11-13T21:05:31Z","timestamp":1194987931000},"page":"182-189","source":"Crossref","is-referenced-by-count":37,"title":["Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development"],"prefix":"10.1210","volume":"93","author":[{"given":"Miroslav","family":"Dumic","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes (M.D., R.L.), University Hospital Rebro, Zagreb, Croatia 41000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lin-Su","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology\/Division of Adrenal Steroid Disorders (K.L.-S., S.N., M.I.N.), Mount Sinai School of Medicine, New York, New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha I.","family":"Leibel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology (N.I.L.), Columbia University, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srecko","family":"Ciglar","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics (S.C.), Clinical Hospital Merkur, Zagreb, Croatia 10000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Vinci","sequence":"additional","affiliation":[{"name":"Reproduction, Fertility, and Populations (G.V., K.M.), Institut Pasteur, 75724 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruzica","family":"Lasan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes (M.D., R.L.), University Hospital Rebro, Zagreb, Croatia 41000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saroj","family":"Nimkarn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology\/Division of Adrenal Steroid Disorders (K.L.-S., S.N., M.I.N.), Mount Sinai School of Medicine, New York, New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Endocrinology (J.D.W.), University of Texas Southwestern Medical School, Dallas, Texas 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"McElreavey","sequence":"additional","affiliation":[{"name":"Reproduction, Fertility, and Populations (G.V., K.M.), Institut Pasteur, 75724 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"New","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology\/Division of Adrenal Steroid Disorders (K.L.-S., S.N., M.I.N.), Mount Sinai School of Medicine, New York, New York 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613570499100_R1","first-page":"263","article-title":"Clinical and DNA studies on 46,XY females with gonadal dysgenesis. A report of six cases.","volume":"41","author":"Kucheria","year":"1996","journal-title":"J Reprod Med"},{"key":"2020071613570499100_R2","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","year":"1990","journal-title":"Nature"},{"key":"2020071613570499100_R3","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","year":"1990","journal-title":"Nature"},{"key":"2020071613570499100_R4","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1073\/pnas.90.8.3368","article-title":"A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development.","volume":"90","author":"McElreavey","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613570499100_R5","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nature01722","article-title":"The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes.","volume":"423","author":"Skaletsky","year":"2003","journal-title":"Nature"},{"key":"2020071613570499100_R6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ydbio.2004.07.011","article-title":"SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors.","volume":"274","author":"Sekido","year":"2004","journal-title":"Dev Biol"},{"key":"2020071613570499100_R7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1210\/jcem.85.2.6418","article-title":"Clinical review 111: familial sex reversal: a review.","volume":"85","author":"Sarafoglou","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613570499100_R8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1056\/NEJMra022784","article-title":"Sex determination and differentiation.","volume":"350","author":"MacLaughlin","year":"2004","journal-title":"N Engl J Med"},{"key":"2020071613570499100_R9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/dvdy.20042","article-title":"Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis.","volume":"230","author":"Yao","year":"2004","journal-title":"Dev Dyn"},{"key":"2020071613570499100_R10","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1242\/dev.129.19.4627","article-title":"Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2.","volume":"129","author":"Tevosian","year":"2002","journal-title":"Development"},{"key":"2020071613570499100_R11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1515\/JPEM.2005.18.8.739","article-title":"Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature.","volume":"18","author":"Ergun-Longmire","year":"2005","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2020071613570499100_R12","doi-asserted-by":"crossref","first-page":"68S","DOI":"10.1097\/00006250-198409001-00018","article-title":"Complete development of secondary sex characteristics in a case of 46,XY pure gonadal dysgenesis","volume":"64","author":"Villanueva","year":"1984","journal-title":"Obstet Gynecol"},{"key":"2020071613570499100_R13","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0015-0282(16)54843-2","article-title":"Chimerism as the etiology of a 46,XX\/46,XY fertile true hermaphrodite.","volume":"57","author":"Verp","year":"1992","journal-title":"Fertil Steril"},{"key":"2020071613570499100_R14","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.fertnstert.2004.02.129","article-title":"A nonmosaic 45,X karyotype in a mother with Turner\u2019s syndrome and in her daughter.","volume":"82","author":"Cools","year":"2004","journal-title":"Fertil Steril"},{"key":"2020071613570499100_R15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1210\/jcem-33-1-42","article-title":"Radioimmunoassay of plasma 17-hydroxyprogesterone.","volume":"33","author":"Abraham","year":"1971","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613570499100_R16","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/S0009-9120(75)93886-2","article-title":"Combined radioimmunoassay of four steroids in one ml of plasma. II. Androgens.","volume":"8","author":"Abraham","year":"1975","journal-title":"Clin Biochem"},{"key":"2020071613570499100_R17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/jcem-42-1-117","article-title":"Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche.","volume":"42","author":"Korth-Schutz","year":"1976","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613570499100_R18","first-page":"749","article-title":"A recent insertion of an alu element on the Y chromosome is a useful marker for human population studies","volume":"Evol","author":"Hammer","year":"1994","journal-title":"Mol Biol"},{"key":"2020071613570499100_R19","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1086\/321210","article-title":"A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy","volume":"Genet","author":"Umehara","year":"2000","journal-title":"Am J Hum"},{"key":"2020071613570499100_R20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1677\/jme.0.0170139","article-title":"Cloning and sequence analysis of the human gene encoding steroidogenic factor 1.","volume":"17","author":"Wong","year":"1996","journal-title":"J Mol Endocrinol"},{"key":"2020071613570499100_R21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ajmg.1320270308","article-title":"Phenotypic spectrum of 45,X\/46,XY individuals.","volume":"27","author":"Rosenberg","year":"1987","journal-title":"Am J Med Genet"},{"key":"2020071613570499100_R22","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1023\/B:JARG.0000040239.40913.c3","article-title":"Spontaneous pregnancies in a Turner syndrome woman with Y-chromosome mosaicism.","volume":"21","author":"Landin-Wilhelmsen","year":"2004","journal-title":"J Assist Reprod Genet"},{"key":"2020071613570499100_R23","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1023\/A:1009273205788","article-title":"XY sex reversal in the wood lemming is associated with deletion of Xp21\u201323 as revealed by chromosome microdissection and fluorescence in situ hybridization.","volume":"6","author":"Liu","year":"1998","journal-title":"Chromosome Res"},{"key":"2020071613570499100_R24","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1006\/dbio.1996.0217","article-title":"Competence of oocytes from the B6.YDOM sex-reversed female mouse for maturation, fertilization, and embryonic development in vitro.","volume":"178","author":"Amleh","year":"1996","journal-title":"Dev Biol"},{"key":"2020071613570499100_R25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1530\/jrf.0.0580157","article-title":"H-Y antigen in a fertile XY female horse.","volume":"58","author":"Sharp","year":"1980","journal-title":"J Reprod Fertil"},{"key":"2020071613570499100_R26","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1136\/jmg.33.9.800","article-title":"Evidence to exclude SOX9 as a candidate gene for XY sex reversal without skeletal malformation.","volume":"33","author":"Kwok","year":"1996","journal-title":"J Med Genet"},{"key":"2020071613570499100_R27","doi-asserted-by":"crossref","first-page":"11689","DOI":"10.1073\/pnas.0401194101","article-title":"Mapping of a sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.","volume":"101","author":"Puffenberger","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613570499100_R28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/84781","article-title":"The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis\/ptosis\/epicanthus inversus syndrome.","volume":"27","author":"Crisponi","year":"2001","journal-title":"Nat Genet"},{"key":"2020071613570499100_R29","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1242\/dev.01890","article-title":"Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells.","volume":"132","author":"Bouma","year":"2005","journal-title":"Development"},{"key":"2020071613570499100_R30","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1086\/320125","article-title":"Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.","volume":"68","author":"Jordan","year":"2001","journal-title":"Am J Hum Genet"},{"key":"2020071613570499100_R31","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ydbio.2004.08.049","article-title":"Wnt4 is required for proper male as well as female sexual development.","volume":"276","author":"Jeays-Ward","year":"2004","journal-title":"Dev Biol"},{"key":"2020071613570499100_R32","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1210\/jc.2004-0863","article-title":"Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis.","volume":"89","author":"Canto","year":"2004","journal-title":"J Clin Endocrinol Metab [Erratum (2004) 89:5453]"},{"key":"2020071613570499100_R33","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0012-1606(03)00391-9","article-title":"Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave.","volume":"262","author":"Menke","year":"2003","journal-title":"Dev Biol"},{"key":"2020071613570499100_R34","first-page":"3925","article-title":"Expression of transcription factor GATA-4 during human testicular development and disease.","volume":"85","author":"Ketola","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613570499100_R35","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1242\/dev.125.14.2665","article-title":"Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter.","volume":"125","author":"Viger","year":"1998","journal-title":"Development"},{"key":"2020071613570499100_R36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1056\/NEJM197007022830102","article-title":"Familial syndrome of streak gonads and normal male karyotype in five phenotypic females.","volume":"283","author":"Espiner","year":"1970","journal-title":"N Engl J Med"},{"key":"2020071613570499100_R37","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1056\/NEJM196803282781302","article-title":"Familial XY gonadal dysgenesis.","volume":"278","author":"Sternberg","year":"1968","journal-title":"N Engl J Med"},{"key":"2020071613570499100_R38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1126\/science.567843","article-title":"Genetically determined sex-reversal in 46,XY humans.","volume":"202","author":"German","year":"1978","journal-title":"Science"},{"key":"2020071613570499100_R39","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/jmg.20.4.264","article-title":"The X linked recessive form of XY gonadal dysgenesis with a high incidence of gonadal germ cell tumors: clinical and genetic studies.","volume":"20","author":"Mann","year":"1983","journal-title":"J Med Genet"},{"key":"2020071613570499100_R40","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1210\/jc.2006-0950","article-title":"A novel human sex-determining gene linked to Xp11.21\u201311.23.","volume":"91","author":"Rajender","year":"2006","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/1\/182\/9053527\/jcem0182.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/1\/182\/9053527\/jcem0182.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T11:43:52Z","timestamp":1630064632000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/1\/182\/2598461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-2155","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,1]]}}}