{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T03:29:47Z","timestamp":1779247787134,"version":"3.51.4"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014476","name":"Pfizer Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014476","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Medical Center Rotterdam"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pituitary"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Congenital hypopituitarism (CH) can cause significant morbidity or even mortality. In the majority of patients, the etiology of CH is unknown. Understanding the etiology of CH is important for anticipation of clinical problems and for genetic counselling. Our previous studies showed that only a small proportion of cases have mutations in the known \u2018CH genes\u2019. In the current project, we present the results of SNP array based copy number variant analysis in a family with unexplained congenital hypopituitarism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA samples of two affected brothers with idiopathic CH and their mother were simultaneously analyzed by SNP arrays for copy number variant analysis and Whole Exome Sequencing (WES) for mutation screening. DNA of the father was not available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a 6\u00a0Mb duplication including<jats:italic>GPR101<\/jats:italic>and<jats:italic>SOX3<\/jats:italic>on the X-chromosome (Xq26.2-q27.1) in the two siblings and their mother, leading to 2 copies of this region in the affected boys and 3 copies in the mother. Duplications of<jats:italic>GPR101<\/jats:italic>are associated with X-linked acrogigantism (the phenotypic \u2018opposite\u2019 of the affected brothers), whereas alterations in<jats:italic>SOX3<\/jats:italic>are associated with X-linked hypopituitarism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In our patients with hypopituitarism we found a 6\u00a0Mb duplication which includes<jats:italic>GPR101<\/jats:italic>, a gene associated with X- linked gigantism, and<jats:italic>SOX3<\/jats:italic>, a gene involved in early pituitary organogenesis that is associated with variable degrees of hypopituitarism. Our findings show that in duplications containing both<jats:italic>GPR101<\/jats:italic>and<jats:italic>SOX3<\/jats:italic>, the growth hormone deficiency phenotype is dominant. This suggests that, if<jats:italic>GPR101<\/jats:italic>is duplicated, it might not be expressed phenotypically when early patterning of the embryonic pituitary is affected due to<jats:italic>SOX3<\/jats:italic>duplication. These results, together with the review of the literature, shed a new light on the role of<jats:italic>GPR101<\/jats:italic>and<jats:italic>SOX3<\/jats:italic>in pituitary function.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s11102-020-01101-8","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T04:50:03Z","timestamp":1605243003000},"page":"229-241","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Congenital hypopituitarism in two brothers with a duplication of the \u2018acrogigantism gene\u2019 GPR101: clinical findings and review of the literature"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7899-2113","authenticated-orcid":false,"given":"Melitza S. M.","family":"Elizabeth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke J. M. H.","family":"Verkerk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita C. S.","family":"Hokken-Koelega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost A. M.","family":"Verlouw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Pfaeffle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian J. C. M. M.","family":"Neggers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny A.","family":"Visser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura C. G.","family":"de Graaff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"1101_CR1","first-page":"1","volume":"45","author":"C Meazza","year":"2013","unstructured":"Meazza C et al (2013) Metabolic parameters and adipokine profi le in growth hormone deficient (GHD) children before and after 12-month GH treatment. Horm Metab Res 45:1\u20135","journal-title":"Horm Metab Res"},{"issue":"9","key":"1101_CR2","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1210\/en.2018-00563","volume":"159","author":"JL Youngblood","year":"2018","unstructured":"Youngblood JL, Coleman TF, Davis SW (2018) Regulation of pituitary progenitor differentiation by beta-catenin. Endocrinology 159(9):3287\u20133305","journal-title":"Endocrinology"},{"issue":"4","key":"1101_CR3","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3803\/EnM.2015.30.4.443","volume":"30","author":"SY Kim","year":"2015","unstructured":"Kim SY (2015) Diagnosis and treatment of hypopituitarism. Endocrinol Metab (Seoul) 30(4):443\u2013455","journal-title":"Endocrinol Metab (Seoul)"},{"key":"1101_CR4","unstructured":"De Graaff L (2008) Genetic and non-genetic causes of isolated growth hormone deficiency and combined pituitary hormone deficiency: results of the HYPOPIT study"},{"issue":"3","key":"1101_CR5","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1210\/er.2013-1067","volume":"35","author":"KS Alatzoglou","year":"2014","unstructured":"Alatzoglou KS et al (2014) Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent advances. Endocr Rev 35(3):376\u2013432","journal-title":"Endocr Rev"},{"issue":"6","key":"1101_CR6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1055\/s-0042-100733","volume":"48","author":"F Castinetti","year":"2016","unstructured":"Castinetti F et al (2016a) GPR101 mutations are not a frequent cause of congenital isolated growth hormone deficiency. Horm Metab Res 48(6):389\u2013393","journal-title":"Horm Metab Res"},{"issue":"1","key":"1101_CR7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.clp.2017.11.001","volume":"45","author":"JS Parks","year":"2018","unstructured":"Parks JS (2018) Congenital hypopituitarism. Clin Perinatol 45(1):75\u201391","journal-title":"Clin Perinatol"},{"issue":"6","key":"1101_CR8","doi-asserted-by":"crossref","first-page":"R239","DOI":"10.1530\/EJE-15-1095","volume":"174","author":"F Castinetti","year":"2016","unstructured":"Castinetti F et al (2016b) Mechanisms in endocrinology: an update in the genetic aetiologies of combined pituitary hormone deficiency. Eur J Endocrinol 174(6):R239\u2013R247","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"1101_CR9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/cen.12000","volume":"78","author":"D Gorbenko del Blanco","year":"2013","unstructured":"Gorbenko del Blanco D et al (2013) Single-nucleotide variants in two Hedgehog genes, SHH and HHIP, as genetic cause of combined pituitary hormone deficiency. Clin Endocrinol (Oxf) 78(3):415\u2013423","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"3","key":"1101_CR10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1530\/EJE-12-0333","volume":"167","author":"D Gorbenko Del Blanco","year":"2012","unstructured":"Gorbenko Del Blanco D et al (2012) A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve. Eur J Endocrinol 167(3):441\u2013452","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"1101_CR11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1159\/000308169","volume":"73","author":"LC de Graaff","year":"2010","unstructured":"de Graaff LC et al (2010) PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1\/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Horm Res Paediatr 73(5):363\u2013371","journal-title":"Horm Res Paediatr"},{"issue":"1","key":"1101_CR12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s11102-017-0850-6","volume":"21","author":"M Elizabeth","year":"2018","unstructured":"Elizabeth M et al (2018) Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies. Pituitary 21(1):76\u201383","journal-title":"Pituitary"},{"issue":"3","key":"1101_CR13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cell.2008.08.040","volume":"135","author":"JB Regard","year":"2008","unstructured":"Regard JB, Sato IT, Coughlin SR (2008) Anatomical profiling of G protein-coupled receptor expression. Cell 135(3):561\u2013571","journal-title":"Cell"},{"issue":"1","key":"1101_CR14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0378-1119(01)00651-5","volume":"275","author":"DK Lee","year":"2001","unstructured":"Lee DK et al (2001) Discovery and mapping of ten novel G protein-coupled receptor genes. Gene 275(1):83\u201391","journal-title":"Gene"},{"key":"1101_CR15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2006.02.123","volume":"1087","author":"B Bates","year":"2006","unstructured":"Bates B et al (2006) Characterization of Gpr101 expression and G-protein coupling selectivity. Brain Res 1087:1\u201314","journal-title":"Brain Res"},{"issue":"25","key":"1101_CR16","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa1408028","volume":"371","author":"G Trivellin","year":"2014","unstructured":"Trivellin G et al (2014) Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med 371(25):2363\u20132374","journal-title":"N Engl J Med"},{"issue":"3","key":"1101_CR17","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1530\/ERC-15-0038","volume":"22","author":"A Beckers","year":"2015","unstructured":"Beckers A et al (2015) X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer 22(3):353\u2013367","journal-title":"Endocr Relat Cancer"},{"issue":"1","key":"1101_CR18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40478-016-0328-1","volume":"4","author":"D Iacovazzo","year":"2016","unstructured":"Iacovazzo D et al (2016) Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun 4(1):56","journal-title":"Acta Neuropathol Commun"},{"key":"1101_CR19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ghir.2016.09.007","volume":"30\u201331","author":"D Iacovazzo","year":"2016","unstructured":"Iacovazzo D, Korbonits M (2016) Gigantism: X-linked acrogigantism and GPR101 mutations. Growth Horm IGF Res 30\u201331:64\u201369","journal-title":"Growth Horm IGF Res"},{"issue":"3","key":"1101_CR20","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S0959-437X(97)80147-5","volume":"7","author":"LH Pevny","year":"1997","unstructured":"Pevny LH, Lovell-Badge R (1997) Sox genes find their feet. Curr Opin Genet Dev 7(3):338\u2013344","journal-title":"Curr Opin Genet Dev"},{"issue":"1","key":"1101_CR21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2478\/bjmg-2019-0006","volume":"22","author":"V Tasic","year":"2019","unstructured":"Tasic V et al (2019) Duplication of the SOX3 gene in an sry-negative 46, XX male with associated congenital anomalies of kidneys and the urinary tract: case report and review of the literature. Balkan J Med Genet 22(1):81\u201388","journal-title":"Balkan J Med Genet"},{"issue":"2","key":"1101_CR22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1242\/dev.122.2.509","volume":"122","author":"J Collignon","year":"1996","unstructured":"Collignon J et al (1996) A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Development 122(2):509\u2013520","journal-title":"Development"},{"issue":"4","key":"1101_CR23","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0168-9525(99)01955-1","volume":"16","author":"Y Kamachi","year":"2000","unstructured":"Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16(4):182\u2013187","journal-title":"Trends Genet"},{"issue":"5","key":"1101_CR24","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1086\/430134","volume":"76","author":"KS Woods","year":"2005","unstructured":"Woods KS et al (2005) Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism. Am J Hum Genet 76(5):833\u2013849","journal-title":"Am J Hum Genet"},{"issue":"6","key":"1101_CR25","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s11102-013-0546-5","volume":"17","author":"M Takagi","year":"2014","unstructured":"Takagi M et al (2014) A novel mutation in SOX3 polyalanine tract: a case of Kabuki syndrome with combined pituitary hormone deficiency harboring double mutations in MLL2 and SOX3. Pituitary 17(6):569\u2013574","journal-title":"Pituitary"},{"issue":"12","key":"1101_CR26","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.biocel.2007.05.019","volume":"39","author":"V Lefebvre","year":"2007","unstructured":"Lefebvre V et al (2007) Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol 39(12):2195\u20132214","journal-title":"Int J Biochem Cell Biol"},{"issue":"4","key":"1101_CR27","first-page":"910","volume":"60","author":"M Lagerstr\u00f6m-Ferm\u00e9r","year":"1997","unstructured":"Lagerstr\u00f6m-Ferm\u00e9r M et al (1997) X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26. Am J Hum Genet 60(4):910\u2013916","journal-title":"Am J Hum Genet"},{"issue":"4","key":"1101_CR28","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1006\/geno.2002.6741","volume":"79","author":"NM Solomon","year":"2002","unstructured":"Solomon NM et al (2002) Increased gene dosage at Xq26-q27 is associated with X-linked hypopituitarism. Genomics 79(4):553\u2013559","journal-title":"Genomics"},{"issue":"3","key":"1101_CR29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/(SICI)1096-8628(19980319)76:3<255::AID-AJMG10>3.0.CO;2-G","volume":"76","author":"M Raynaud","year":"1998","unstructured":"Raynaud M et al (1998) X-linked mental retardation with isolated growth hormone deficiency is mapped to Xq22-Xq27.2 in one family. Am J Med Genet 76(3):255\u2013261","journal-title":"Am J Med Genet"},{"issue":"2","key":"1101_CR30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1006\/geno.2000.6327","volume":"69","author":"FA Hol","year":"2000","unstructured":"Hol FA et al (2000) Identification and characterization of an Xq26-q27 duplication in a family with spina bifida and panhypopituitarism suggests the involvement of two distinct genes. Genomics 69(2):174\u2013181","journal-title":"Genomics"},{"issue":"1","key":"1101_CR31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q","volume":"64","author":"BC Hamel","year":"1996","unstructured":"Hamel BC et al (1996) Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings. Am J Med Genet 64(1):35\u201341","journal-title":"Am J Med Genet"},{"key":"1101_CR32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4274\/jpr.galenos.2018.83097","volume":"6","author":"VB Arya","year":"2019","unstructured":"Arya VB et al (2019) Xq27.1 Duplication encompassing SOX3: variable phenotype and smallest duplication associated with hypopituitarism to date - a large case series of unrelated patients and a literature review. Horm Res Paediatr 6:1\u20138","journal-title":"Horm Res Paediatr"},{"issue":"6","key":"1101_CR33","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1086\/344661","volume":"71","author":"F Laumonnier","year":"2002","unstructured":"Laumonnier F et al (2002) Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. Am J Hum Genet 71(6):1450\u20131455","journal-title":"Am J Hum Genet"},{"key":"1101_CR34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.mce.2018.08.006","volume":"478","author":"T Yu","year":"2018","unstructured":"Yu T et al (2018) Increased transactivation and impaired repression of beta-catenin-mediated transcription associated with a novel SOX3 missense mutation in an X-linked hypopituitarism pedigree with modest growth failure. Mol Cell Endocrinol 478:133\u2013140","journal-title":"Mol Cell Endocrinol"},{"issue":"3","key":"1101_CR35","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejmg.2017.11.012","volume":"61","author":"AM Jelsig","year":"2018","unstructured":"Jelsig AM et al (2018) A complex phenotype in a family with a pathogenic SOX3 missense variant. Eur J Med Genet 61(3):168\u2013172","journal-title":"Eur J Med Genet"},{"issue":"4","key":"1101_CR36","doi-asserted-by":"crossref","first-page":"E685","DOI":"10.1210\/jc.2010-1239","volume":"96","author":"KS Alatzoglou","year":"2011","unstructured":"Alatzoglou KS et al (2011) Increased transactivation associated with SOX3 polyalanine tract deletion in a patient with hypopituitarism. J Clin Endocrinol Metab 96(4):E685\u2013E690","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1101_CR37","first-page":"552","volume":"13","author":"S Stagi","year":"2014","unstructured":"Stagi S et al (2014) A SOX3 (Xq26.3\u201327.3) duplication in a boy with growth hormone deficiency, ocular dyspraxia, and intellectual disability: a long-term follow-up and literature review. Hormones (Athens) 13(4):552\u2013560","journal-title":"Hormones (Athens)"},{"issue":"11","key":"1101_CR38","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/pd.5523","volume":"39","author":"M Hureaux","year":"2019","unstructured":"Hureaux M et al (2019) SOX3 duplication: a genetic cause to investigate in fetuses with neural tube defects. Prenat Diagn 39(11):1026\u20131034","journal-title":"Prenat Diagn"},{"key":"1101_CR39","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/ajmg.a.36580","volume":"164","author":"M Bauters","year":"2014","unstructured":"Bauters M et al (2014) Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects. Am J Med Genet A 164:1947","journal-title":"Am J Med Genet A"},{"issue":"1","key":"1101_CR40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ajmg.a.30910","volume":"138","author":"P Stankiewicz","year":"2005","unstructured":"Stankiewicz P et al (2005) Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia. Am J Med Genet A 138(1):11\u201317","journal-title":"Am J Med Genet A"},{"key":"1101_CR41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/cen.13126","volume":"85","author":"R Grinspon","year":"2016","unstructured":"Grinspon R et al (2016) 46, XX ovotesticular DSD associated with a SOX3 gene duplication in a SRY -negative boy. Clin Endocrinol 85:673","journal-title":"Clin Endocrinol"},{"issue":"3","key":"1101_CR42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000377653","volume":"9","author":"M Igarashi","year":"2015","unstructured":"Igarashi M et al (2015) SOX3 overdosage permits normal sex development in females with random X inactivation. Sex Dev 9(3):125\u2013129","journal-title":"Sex Dev"},{"issue":"7","key":"1101_CR43","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1002\/ajmg.a.37072","volume":"167","author":"A Uguen","year":"2015","unstructured":"Uguen A et al (2015) Duplication of SOX3 (Xq27) may be a risk factor for neural tube defects. Am J Med Genet A 167(7):1676\u20131678","journal-title":"Am J Med Genet A"},{"issue":"3","key":"1101_CR44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1515\/jpem-2015-0131","volume":"33","author":"ET Rosolowsky","year":"2020","unstructured":"Rosolowsky ET et al (2020) Marked phenotypic variable expression among brothers with duplication of Xq27.1 involving the SOX3 gene. J Pediatr Endocrinol Metab 33(3):443\u2013447","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"5","key":"1101_CR45","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/ajmg.a.35823","volume":"161","author":"JR Helle","year":"2013","unstructured":"Helle JR et al (2013) Hyperphagia, mild developmental delay but apparently no structural brain anomalies in a boy without SOX3 expression. Am J Med Genet A 161(5):1137\u20131142","journal-title":"Am J Med Genet A"},{"issue":"7","key":"1101_CR46","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1002\/ajmg.a.35390","volume":"158","author":"S Moalem","year":"2012","unstructured":"Moalem S et al (2012) XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication. Am J Med Genet A 158(7):1759\u20131764","journal-title":"Am J Med Genet A"},{"issue":"1","key":"1101_CR47","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1172\/JCI42580","volume":"121","author":"E Sutton","year":"2011","unstructured":"Sutton E et al (2011) Identification of SOX3 as an XX male sex reversal gene in mice and humans. J Clin Invest 121(1):328\u2013341","journal-title":"J Clin Invest"},{"issue":"1","key":"1101_CR48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s004390050910","volume":"104","author":"J Gecz","year":"1999","unstructured":"Gecz J et al (1999) Fibroblast growth factor homologous factor 2 (FHF2): gene structure, expression and mapping to the B\u00f6rjeson-Forssman-Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS-like patient. Hum Genet 104(1):56\u201363","journal-title":"Hum Genet"},{"issue":"4","key":"1101_CR49","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/MCD.0b013e32832d06f0","volume":"18","author":"EMM Burkitt Wright","year":"2009","unstructured":"Burkitt Wright EMM et al (2009) X-linked isolated growth hormone deficiency: expanding the phenotypic spectrum of SOX3 polyalanine tract expansions. Clin Dysmorphol 18(4):218\u2013221","journal-title":"Clin Dysmorphol"}],"container-title":["Pituitary"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-020-01101-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11102-020-01101-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-020-01101-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T23:01:49Z","timestamp":1669590109000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11102-020-01101-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,13]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["1101"],"URL":"https:\/\/doi.org\/10.1007\/s11102-020-01101-8","relation":{},"ISSN":["1386-341X","1573-7403"],"issn-type":[{"value":"1386-341X","type":"print"},{"value":"1573-7403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,13]]},"assertion":[{"value":"23 October 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2020","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All procedures performed in this study were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. We obtained approval from the medical ethics committees of all participating hospitals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from the individuals participating in this study and their parents if they were younger than 18\u00a0years.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}