{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:41Z","timestamp":1784557001745,"version":"3.55.0"},"reference-count":54,"publisher":"Bioscientifica","issue":"10","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7,26]]},"abstract":"<jats:p>\n                    Diagnosis and management strategy of disorders of sex development (DSD) are difficult and various due to heterogeneous phenotype and genotype. Under widespread use of genomic sequencing technologies, multiple genes and mechanisms have been identified and proposed as genetic causes of 46,XY DSD. In this study, 178 46,XY DSD patients were enrolled and underwent gene sequencing (either whole-exome sequencing or targeted panel gene sequencing). Detailed clinical phenotype and genotype information were summarized which showed that the most common clinical manifestations were micropenis (56.74%, 101\/178), cryptorchidism (34.27%, 61\/178), and hypospadias (17.42%, 31\/178). Androgen synthesis\/action disorders and idiopathic hypogonadotropic hypogonadism were the most frequent clinical diagnoses, accounting, respectively, for 40.90 and 21.59%. From all next-generation sequencing results, 103 candidate variants distributed across 32 genes were identified in 88 patients. The overall molecular detection rate was 49.44% (88\/178), including 35.96% (64\/178) pathogenic\/likely pathogenic variants and 13.48% (24\/178) variants of uncertain significance. Of all, 19.42% (20\/103) variants were first reported in 46,XY DSD patients. Mutation c.680G&gt;A (p.R227Q) on\n                    <jats:italic>SRD5A2<\/jats:italic>\n                    (steroid 5-alpha-reductase 2) (36.67%, 11\/30) was a hotspot mutation in the Chinese population. Novel candidate genes related to DSD (\n                    <jats:italic>GHR<\/jats:italic>\n                    (growth hormone receptor) and\n                    <jats:italic>PHIP<\/jats:italic>\n                    (pleckstrin homology domain-interacting protein)) were identified. Overall, this was a large cohort of 46,XY DSD patients with a common clinical classification and phenotype spectrum of Chinese patients. Targeted gene panel sequencing covered most of the genes contributing to DSD, whereas whole-exome sequencing detected more candidate genes.\n                  <\/jats:p>","DOI":"10.1530\/ec-23-0029","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T10:07:04Z","timestamp":1690366024000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":15,"title":["Clinical characteristics and genetic expansion of 46,XY disorders of sex development children in a Chinese prospective study"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-6446","authenticated-orcid":true,"given":"Yijun","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3391-5250","authenticated-orcid":true,"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-759X","authenticated-orcid":true,"given":"Xiumin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Clinical Endocrinology","first-page":"634","article-title":"Health-related quality of life and psychological well-being in adults with differences\/disorders of sex development","volume":"86","author":"Bennecke","year":"2017","unstructured":"Bennecke EThyen UGr\u00fcters ALux A & K\u00f6hler B. Health-related quality of life and psychological well-being in adults with differences\/disorders of sex development. Clinical Endocrinology201786634\u2013643. (https:\/\/doi.org\/10.1111\/cen.13296)"},{"key":"bib2","series-title":"Archives of Disease in Childhood","first-page":"554","article-title":"Consensus statement on management of intersex disorders","volume":"91","author":"Hughes","year":"2006","unstructured":"Hughes IAHouk CAhmed SFLee PA, LWPES Consensus Group & ESPE Consensus Group. Consensus statement on management of intersex disorders. Archives of Disease in Childhood200691554\u2013563. (https:\/\/doi.org\/10.1136\/adc.2006.098319)"},{"key":"bib3","series-title":"BMC Public Health","first-page":"110","article-title":"Clinical evaluation study of the German network of disorders of sex development (DSD)\/intersexuality: study design, description of the study population, and data quality","volume":"9","author":"Lux","year":"2009","unstructured":"Lux AKropf SKleinemeier EJ\u00fcrgensen MThyen U & DSD Network Working Group. Clinical evaluation study of the German network of disorders of sex development (DSD)\/intersexuality: study design, description of the study population, and data quality. BMC Public Health20099110. (https:\/\/doi.org\/10.1186\/1471-2458-9-110)"},{"key":"bib4","series-title":"BMC Urology","first-page":"21","article-title":"Evaluation and treatment for ovotesticular disorder of sex development (OT-DSD) - experience based on a Chinese series","volume":"17","author":"Mao","year":"2017","unstructured":"Mao YChen SWang RWang XQin D & Tang Y. Evaluation and treatment for ovotesticular disorder of sex development (OT-DSD) - experience based on a Chinese series. BMC Urology20171721. (https:\/\/doi.org\/10.1186\/s12894-017-0212-8)"},{"key":"bib5","series-title":"Asian Journal of Andrology","first-page":"69","article-title":"Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing","volume":"23","author":"Yu","year":"2021","unstructured":"Yu BQLiu ZXGao YJWang XMao JFNie M & Wu XY. Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing. Asian Journal of Andrology20212369\u201373. (https:\/\/doi.org\/10.4103\/aja.aja_36_20)"},{"key":"bib6","series-title":"Nature Reviews. Endocrinology","first-page":"520","article-title":"Management of disorders of sex development","volume":"10","author":"Hiort","year":"2014","unstructured":"Hiort OBirnbaum WMarshall LW\u00fcnsch LWerner RSchr\u00f6der TD\u00f6hnert U & Holterhus PM. Management of disorders of sex development. Nature Reviews. Endocrinology201410520\u2013529. (https:\/\/doi.org\/10.1038\/nrendo.2014.108)"},{"key":"bib7","series-title":"Nature Reviews. Endocrinology","first-page":"79","article-title":"Disorders of sex development: new genes, new concepts","volume":"9","author":"Ono","year":"2013","unstructured":"Ono M & Harley VR. Disorders of sex development: new genes, new concepts. Nature Reviews. Endocrinology2013979\u201391. (https:\/\/doi.org\/10.1038\/nrendo.2012.235)"},{"key":"bib8","series-title":"Lancet. Diabetes and Endocrinology","first-page":"560","article-title":"A clinical algorithm to diagnose differences of sex development","volume":"7","author":"Le\u00f3n","year":"2019","unstructured":"Le\u00f3n NYReyes AP & Harley VR. A clinical algorithm to diagnose differences of sex development. Lancet. Diabetes and Endocrinology20197560\u2013574. (https:\/\/doi.org\/10.1016\/S2213-8587(1830339-5)"},{"key":"bib9","series-title":"Frontiers in Endocrinology","first-page":"839895","article-title":"Difference of precocious puberty between before and during the COVID-19 pandemic: a cross-sectional study among shanghai school-aged girls","volume":"13","author":"Chen","year":"2022","unstructured":"Chen YChen JTang YZhang QWang YLi QLi XWeng ZHuang JWang X, Difference of precocious puberty between before and during the COVID-19 pandemic: a cross-sectional study among shanghai school-aged girls. Frontiers in Endocrinology202213839895. (https:\/\/doi.org\/10.3389\/fendo.2022.839895)"},{"key":"bib10","series-title":"Environment International","first-page":"410","article-title":"Association between bisphenol A exposure and idiopathic central precocious puberty (ICPP) among school-aged girls in Shanghai, China","volume":"115","author":"Chen","year":"2018","unstructured":"Chen YWang YDing GTian YZhou ZWang XShen L & Huang H. Association between bisphenol A exposure and idiopathic central precocious puberty (ICPP) among school-aged girls in Shanghai, China. Environment International2018115410\u2013416. (https:\/\/doi.org\/10.1016\/j.envint.2018.02.041)"},{"key":"bib11","series-title":"Human Growth","article-title":"The methods of axiological anthropometry","author":"Cameron","year":"1978","unstructured":"Cameron N. The methods of axiological anthropometry. In Human Growth2nd ed.FanlknerF & TannerJM, Eds. London: Plenum Press1978."},{"key":"bib12","series-title":"Archives of Disease in Childhood","first-page":"291","article-title":"Variations in pattern of pubertal changes in girls","volume":"44","author":"Marshall","year":"1969","unstructured":"Marshall WA & Tanner JM. Variations in pattern of pubertal changes in girls. Archives of Disease in Childhood196944291\u2013303. (https:\/\/doi.org\/10.1136\/adc.44.235.291)"},{"key":"bib13","series-title":"Radiographic Atlas of Skeletal Development of the Hand and Wrist","first-page":"518","author":"Greulich","year":"1959","unstructured":"Greulich WW & Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd ed., pp. 518\u2013520Stanford: Stanford University Press1959."},{"key":"bib14","series-title":"Chonnam Medical Journal","first-page":"70","article-title":"The diagnostic value of pelvic ultrasound in girls with central precocious puberty","volume":"52","author":"Lee","year":"2016","unstructured":"Lee SHJoo EYLee JEJun YH & Kim MY. The diagnostic value of pelvic ultrasound in girls with central precocious puberty. Chonnam Medical Journal20165270\u201374. (https:\/\/doi.org\/10.4068\/cmj.2016.52.1.70)"},{"key":"bib15","series-title":"Chemical Senses","first-page":"189","article-title":"Development of the Chinese smell identification test","volume":"44","author":"Feng","year":"2019","unstructured":"Feng GZhuang YYao FYe YWan Q & Zhou W. Development of the Chinese smell identification test. Chemical Senses201944189\u2013195. (https:\/\/doi.org\/10.1093\/chemse\/bjz006)"},{"key":"bib16","series-title":"Frontiers in Neuroscience","first-page":"842","article-title":"Brain structural correlates of odor identification in mild cognitive impairment and Alzheimer's disease revealed by magnetic resonance imaging and a Chinese olfactory identification test","volume":"13","author":"Wu","year":"2019","unstructured":"Wu XGeng ZZhou SBai TWei LJi GJZhu WYu YTian Y & Wang K. Brain structural correlates of odor identification in mild cognitive impairment and Alzheimer's disease revealed by magnetic resonance imaging and a Chinese olfactory identification test. Frontiers in Neuroscience201913842. (https:\/\/doi.org\/10.3389\/fnins.2019.00842)"},{"key":"bib17","series-title":"Frontiers in Genetics","first-page":"808919","article-title":"Molecular and phenotypic expansion of Alstr\u00f6m syndrome in Chinese patients","volume":"13","author":"Zhang","year":"2022","unstructured":"Zhang QDing YFeng BTang YChen YWang YChang GLiu SWang JLi Q, Molecular and phenotypic expansion of Alstr\u00f6m syndrome in Chinese patients. Frontiers in Genetics202213808919. (https:\/\/doi.org\/10.3389\/fgene.2022.808919)"},{"key":"bib18","series-title":"Journal of Pediatric Endocrinology and Metabolism","first-page":"337","article-title":"The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche","volume":"29","author":"\u00d6zgen","year":"2016","unstructured":"\u00d6zgen \u0130TTorun EBayraktar-Tanyeri BDurmaz EK\u0131l\u0131\u00e7 E & Cesur Y. The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche. Journal of Pediatric Endocrinology and Metabolism201629337\u2013341. (https:\/\/doi.org\/10.1515\/jpem-2015-0235)"},{"key":"bib19","series-title":"European Journal of Endocrinology","first-page":"311","article-title":"New insights from unbiased panel and whole-exome sequencing in a large Chinese cohort with disorders of sex development","volume":"181","year":"2019","unstructured":"Xu Y, Wang Y, Li N, Yao R, Li G, Li J, Ding Y, Chen Y, Huang X, Chen Y, New insights from unbiased panel and whole-exome sequencing in a large Chinese cohort with disorders of sex development. European Journal of Endocrinology2019181311\u2013323. (https:\/\/doi.org\/10.1530\/EJE-19-0111)"},{"key":"bib20","series-title":"American Journal of Medical Genetics","first-page":"365","article-title":"Novel mutation of TBX3 in a Japanese family with ulnar-mammary syndrome: implication for impaired sex development","volume":"110","author":"Sasaki","year":"2002","unstructured":"Sasaki GOgata TIshii THasegawa TSato S & Matsuo N. Novel mutation of TBX3 in a Japanese family with ulnar-mammary syndrome: implication for impaired sex development. American Journal of Medical Genetics2002110365\u2013369. (https:\/\/doi.org\/10.1002\/ajmg.10447)"},{"key":"bib21","series-title":"Obesity Research and Clinical Practice","first-page":"303","article-title":"Chung-Jansen Syndrome with obesity","volume":"15","author":"Kaur","year":"2021","unstructured":"Kaur H & Panigrahi I. Chung-Jansen Syndrome with obesity. Obesity Research and Clinical Practice202115303\u2013305. (https:\/\/doi.org\/10.1016\/j.orcp.2021.03.015)"},{"key":"bib22","series-title":"Reviews in Endocrine and Metabolic Disorders","first-page":"31","article-title":"Laron syndrome: a historical perspective","volume":"22","author":"Laron","year":"2021","unstructured":"Laron Z & Werner H. Laron syndrome: a historical perspective. Reviews in Endocrine and Metabolic Disorders20212231\u201341. (https:\/\/doi.org\/10.1007\/s11154-020-09595-0)"},{"key":"bib23","series-title":"Journal of Cerebral Blood Flow and Metabolism","first-page":"153","article-title":"Phenotypic variability in 446 CADASIL patients: impact of notch3 gene mutation location in addition to the effects of age, sex and vascular risk factors","volume":"43","author":"Dup\u00e9","year":"2023","unstructured":"Dup\u00e9 CGuey SBiard LDieng SLebenberg JGrosset LAlili NHerv\u00e9 DTournier-Lasserve EJouvent E, Phenotypic variability in 446 CADASIL patients: impact of notch3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Journal of Cerebral Blood Flow and Metabolism202343153\u2013166. (https:\/\/doi.org\/10.1177\/0271678X221126280)"},{"key":"bib24","series-title":"Diagnostics (Basel, Switzerland)","first-page":"1379","article-title":"46,XX DSD: developmental, clinical and genetic aspects","volume":"11","author":"Alkhzouz","year":"2021","unstructured":"Alkhzouz CBucerzan SMiclaus MMirea AM & Miclea D. 46,XX DSD: developmental, clinical and genetic aspects. Diagnostics (Basel, Switzerland)2021111379. (https:\/\/doi.org\/10.3390\/diagnostics11081379)"},{"key":"bib25","series-title":"Endokrynologia Polska","first-page":"558","article-title":"Etiological classification and clinical spectrum of Egyptian pediatric patients with disorder of sex development, single center experience","volume":"72","author":"Shamma","year":"2021","unstructured":"Shamma RAAtef S & Arafa N. Etiological classification and clinical spectrum of Egyptian pediatric patients with disorder of sex development, single center experience. Endokrynologia Polska202172558\u2013565. (https:\/\/doi.org\/10.5603\/EP.a2021.0045)"},{"key":"bib26","series-title":"Nature Reviews. Endocrinology","first-page":"415","article-title":"Caring for individuals with a difference of sex development (DSD): a Consensus Statement","volume":"14","author":"Cools","year":"2018","unstructured":"Cools MNordenstr\u00f6m ARobeva RHall JWesterveld PFl\u00fcck CK\u00f6hler BBerra MSpringer ASchweizer K, Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nature Reviews. Endocrinology201814415\u2013429. (https:\/\/doi.org\/10.1038\/s41574-018-0010-8)"},{"key":"bib27","series-title":"Neuroendocrinology","first-page":"959","article-title":"Clinical and genetic characterization of a constitutional delay of growth and puberty cohort","volume":"110","author":"Barroso","year":"2020","unstructured":"Barroso PSJorge AALLerario AMMontenegro LRVasques GALima Amato LGGontijo Silveira LFMendonca BB & Latronico AC. Clinical and genetic characterization of a constitutional delay of growth and puberty cohort. Neuroendocrinology2020110959\u2013966. (https:\/\/doi.org\/10.1159\/000504783)"},{"key":"bib28","series-title":"Andrologia","first-page":"e13250","article-title":"Molecular investigation of mutations in androgen receptor and 5-alpha-reductase-2 genes in 46,XY Disorders of Sex Development with normal testicular development","volume":"51","author":"Ahmadifard","year":"2019","unstructured":"Ahmadifard MKajbafzadeh APanjeh-Shahi SVand-Rajabpour FAhmadi-Beni RArshadi HSetoodeh ARostami PTavakkoly-Bazzaz J & Tabrizi M. Molecular investigation of mutations in androgen receptor and 5-alpha-reductase-2 genes in 46,XY Disorders of Sex Development with normal testicular development. Andrologia201951e13250. (https:\/\/doi.org\/10.1111\/and.13250)"},{"key":"bib29","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1866","article-title":"Pubertal development and pregnancy outcomes in 46,XX patients with nonclassic lipoid congenital adrenal hyperplasia","volume":"104","author":"Hatabu","year":"2019","unstructured":"Hatabu NAmano NMori JHasegawa YMatsuura HSumitomo NNishizawa KSuzuki MKatakura SKanamoto N, Pubertal development and pregnancy outcomes in 46,XX patients with nonclassic lipoid congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism20191041866\u20131870. (https:\/\/doi.org\/10.1210\/jc.2018-01752)"},{"key":"bib30","series-title":"Archives of Sexual Behavior","first-page":"913","article-title":"Early genital surgery in disorders\/differences of sex development: patients' perspectives","volume":"50","author":"Bennecke","year":"2021","unstructured":"Bennecke EBernstein SLee Pvan de Grift TCNordenskj\u00f6ld ARapp MSimmonds MStreuli JCThyen UWiesemann C, Early genital surgery in disorders\/differences of sex development: patients' perspectives. Archives of Sexual Behavior202150913\u2013923. (https:\/\/doi.org\/10.1007\/s10508-021-01953-6)"},{"key":"bib31","series-title":"Annual Review of Clinical Psychology","first-page":"201","article-title":"Differences\/disorders of sex development: medical conditions at the intersection of sex and gender","volume":"18","author":"Sandberg","year":"2022","unstructured":"Sandberg DE & Gardner M. Differences\/disorders of sex development: medical conditions at the intersection of sex and gender. Annual Review of Clinical Psychology202218201\u2013231. (https:\/\/doi.org\/10.1146\/annurev-clinpsy-081219-101412)"},{"key":"bib32","series-title":"Clinical Endocrinology","first-page":"164","article-title":"Long-term outcomes and molecular analysis of a large cohort of patients with 46,XY disorder of sex development due to partial gonadal dysgenesis","volume":"89","author":"Gomes","year":"2018","unstructured":"Gomes NLLer\u00e1rio AMMachado AZMoraes DRSilva TEDArnhold IJPBatista RLFaria J\u00fanior JADCosta EFNishi MY, Long-term outcomes and molecular analysis of a large cohort of patients with 46,XY disorder of sex development due to partial gonadal dysgenesis. Clinical Endocrinology201889164\u2013177. (https:\/\/doi.org\/10.1111\/cen.13717)"},{"key":"bib33","series-title":"Andrology","first-page":"572","article-title":"AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity","volume":"2","author":"Akcay","year":"2014","unstructured":"Akcay TFernandez-Cancio MTuran SG\u00fcran TAudi L & Bereket A. AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity. Andrology20142572\u2013578. (https:\/\/doi.org\/10.1111\/j.2047-2927.2014.00215.x)"},{"key":"bib34","series-title":"Genome Biology","first-page":"243","article-title":"Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort","volume":"17","author":"Eggers","year":"2016","unstructured":"Eggers SSadedin Svan den Bergen JARobevska GOhnesorg THewitt JLambeth LBouty AKnarston IMTan TY, Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biology201617243. (https:\/\/doi.org\/10.1186\/s13059-016-1105-y)"},{"key":"bib35","series-title":"European Urology","first-page":"507","article-title":"How far should we explore hypospadias? Next-generation sequencing applied to a large cohort of hypospadiac patients","volume":"79","author":"Ea","year":"2021","unstructured":"Ea VBergougnoux APhilibert PServant-Fauconnet NFaure ABreaud JGaspari LSultan CParis F & Kalfa N. How far should we explore hypospadias? Next-generation sequencing applied to a large cohort of hypospadiac patients. European Urology202179507\u2013515. (https:\/\/doi.org\/10.1016\/j.eururo.2020.12.036)"},{"key":"bib36","series-title":"Diagnostics (Basel, Switzerland)","first-page":"2107","article-title":"Molecular and cytogenetic analysis of Romanian patients with differences in sex development","volume":"11","author":"Miclea","year":"2021","unstructured":"Miclea DAlkhzouz CBucerzan SGrigorescu-Sido PPopp RAPascanu IMCret VGhervan CBlaga L & Zaharie G. Molecular and cytogenetic analysis of Romanian patients with differences in sex development. Diagnostics (Basel, Switzerland)2021112107. (https:\/\/doi.org\/10.3390\/diagnostics11112107)"},{"key":"bib37","series-title":"Human Genetics","first-page":"265","article-title":"Next-generation sequencing reveals genetic landscape in 46, XY disorders of sexual development patients with variable phenotypes","volume":"137","author":"Wang","year":"2018","unstructured":"Wang HZhang LWang NZhu HHan BSun FYao HZhang QZhu WCheng T, Next-generation sequencing reveals genetic landscape in 46, XY disorders of sexual development patients with variable phenotypes. Human Genetics2018137265\u2013277. (https:\/\/doi.org\/10.1007\/s00439-018-1879-y)"},{"key":"bib38","series-title":"European Journal of Medical Genetics","first-page":"104154","article-title":"A large cohort of disorders of sex development and their genetic characteristics: 6 novel mutations in known genes","volume":"64","author":"Ata","year":"2021","unstructured":"Ata A\u00d6zen SOnay HUzun SG\u00f6k\u015fen D\u00d6zk\u0131nay F\u00d6zbaran NBUlman \u0130 & Darcan \u015e. A large cohort of disorders of sex development and their genetic characteristics: 6 novel mutations in known genes. European Journal of Medical Genetics202164104154. (https:\/\/doi.org\/10.1016\/j.ejmg.2021.104154)"},{"key":"bib39","series-title":"Frontiers in Endocrinology","first-page":"846801","article-title":"Correlation analysis of genotypes and phenotypes in Chinese male pediatric patients with congenital hypogonadotropic hypogonadism","volume":"13","author":"Wang","year":"2022","unstructured":"Wang YQin MFan L & Gong C. Correlation analysis of genotypes and phenotypes in Chinese male pediatric patients with congenital hypogonadotropic hypogonadism. Frontiers in Endocrinology202213846801. (https:\/\/doi.org\/10.3389\/fendo.2022.846801)"},{"key":"bib40","series-title":"Pediatric Endocrinology Reviews","first-page":"34","article-title":"SRD5A2 gene mutations--a population-based review","volume":"8","author":"Samtani","year":"2010","unstructured":"Samtani RBajpai MGhosh PK & Saraswathy KN. SRD5A2 gene mutations--a population-based review. Pediatric Endocrinology Reviews2010834\u201340."},{"key":"bib41","series-title":"Hormones (Athens, Greece)","first-page":"197","article-title":"5-\u03b1-reductase type 2 deficiency: is there a genotype-phenotype correlation? A review","volume":"17","author":"Avenda\u00f1o","year":"2018","unstructured":"Avenda\u00f1o AParadisi ICammarata-Scalisi F & Callea M. 5-\u03b1-reductase type 2 deficiency: is there a genotype-phenotype correlation? A review. Hormones (Athens, Greece)201817197\u2013204. (https:\/\/doi.org\/10.1007\/s42000-018-0013-9)"},{"key":"bib42","series-title":"Molecular Genetics and Genomic Medicine","first-page":"e1431","article-title":"Clinical characteristics and genotype-phenotype correlations of 130 Chinese children in a high-homogeneity single-center cohort with 5\u03b1-reductase 2 deficiency","volume":"8","author":"Fan","year":"2020","unstructured":"Fan LSong YPolak MLi LRen XZhang BWu D & Gong C. Clinical characteristics and genotype-phenotype correlations of 130 Chinese children in a high-homogeneity single-center cohort with 5\u03b1-reductase 2 deficiency. Molecular Genetics and Genomic Medicine20208e1431. (https:\/\/doi.org\/10.1002\/mgg3.1431)"},{"key":"bib43","series-title":"Translational Andrology and Urology","first-page":"137","article-title":"Androgen receptor gene mutation, rearrangement, polymorphism","volume":"2","author":"Eisermann","year":"2013","unstructured":"Eisermann KWang DJing YPascal LE & Wang Z. Androgen receptor gene mutation, rearrangement, polymorphism. Translational Andrology and Urology20132137\u2013147. (https:\/\/doi.org\/10.3978\/j.issn.2223-4683.2013.09.15)"},{"key":"bib44","series-title":"European Review for Medical and Pharmacological Sciences","first-page":"3873","article-title":"Androgen insensitivity syndrome","volume":"22","author":"Gul\u00eda","year":"2018","unstructured":"Gul\u00eda CBaldassarra SZangari ABriganti VGigli SGaffi MSignore FVallone CNucciotti RCostantini FM, Androgen insensitivity syndrome. European Review for Medical and Pharmacological Sciences2018223873\u20133887. (https:\/\/doi.org\/10.26355\/eurrev_201806_15272)"},{"key":"bib45","series-title":"Clinical Case Reports","first-page":"2138","article-title":"A case series of a mother and two daughters with a GLI2 gene deletion demonstrating variable expressivity and incomplete penetrance","volume":"8","author":"Elward","year":"2020","unstructured":"Elward CBerg JOberlin JM & Rohena L. A case series of a mother and two daughters with a GLI2 gene deletion demonstrating variable expressivity and incomplete penetrance. Clinical Case Reports202082138\u20132144. (https:\/\/doi.org\/10.1002\/ccr3.3085)"},{"key":"bib46","series-title":"Journal of Molecular Endocrinology","first-page":"R141","article-title":"Role of GLI2 in hypopituitarism phenotype","volume":"54","author":"Arnhold","year":"2015","unstructured":"Arnhold IJFran\u00e7a MMCarvalho LRMendonca BB & Jorge AA. Role of GLI2 in hypopituitarism phenotype. Journal of Molecular Endocrinology201554R141\u2013R150. (https:\/\/doi.org\/10.1530\/JME-15-0009)"},{"key":"bib47","series-title":"Gynecological Endocrinology","first-page":"296","article-title":"Kallmann syndrome in women: from genes to diagnosis and treatment","volume":"29","author":"Meczekalski","year":"2013","unstructured":"Meczekalski BPodfigurna-Stopa ASmolarczyk RKatulski K & Genazzani AR. Kallmann syndrome in women: from genes to diagnosis and treatment. Gynecological Endocrinology201329296\u2013300. (https:\/\/doi.org\/10.3109\/09513590.2012.752459)"},{"issue":"Supplement 2","key":"bib48","series-title":"Journal of Clinical Research in Pediatric Endocrinology","first-page":"113","article-title":"Update on the genetics of idiopathic hypogonadotropic hypogonadism","volume":"9","author":"Topalo\u011flu","year":"2017","unstructured":"Topalo\u011flu AK. Update on the genetics of idiopathic hypogonadotropic hypogonadism. Journal of Clinical Research in Pediatric Endocrinology20179(Supplement 2) 113\u2013122. (https:\/\/doi.org\/10.4274\/jcrpe.2017.S010)"},{"key":"bib49","series-title":"Frontiers in Endocrinology","first-page":"582516","article-title":"Disorders of sex development in individuals harbouring MAMLD1 variants: WES and interactome evidence of oligogenic inheritance","volume":"11","author":"Li","year":"2020","unstructured":"Li LGao FFan LSu CLiang X & Gong C. Disorders of sex development in individuals harbouring MAMLD1 variants: WES and interactome evidence of oligogenic inheritance. Frontiers in Endocrinology202011582516. (https:\/\/doi.org\/10.3389\/fendo.2020.582516)"},{"key":"bib50","series-title":"Sexual Development","first-page":"147","article-title":"Identification of NR5A1 mutations and possible digenic inheritance in 46,XY gonadal dysgenesis","volume":"10","author":"Mazen","year":"2016","unstructured":"Mazen IAbdel-Hamid MMekkawy MBignon-Topalovic JBoudjenah REl Gammal MEssawi MBashamboo A & McElreavey K. Identification of NR5A1 mutations and possible digenic inheritance in 46,XY gonadal dysgenesis. Sexual Development201610147\u2013151. (https:\/\/doi.org\/10.1159\/000445983)"},{"key":"bib51","series-title":"Human Reproduction Update","first-page":"15","article-title":"A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships","volume":"28","author":"Houston","year":"2021","unstructured":"Houston BJRiera-Escamilla AWyrwoll MJSalas-Huetos AXavier MJNagirnaja LFriedrich CConrad DFAston KIKrausz C, A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships. Human Reproduction Update20212815\u201329. (https:\/\/doi.org\/10.1093\/humupd\/dmab030)"},{"key":"bib52","series-title":"International Journal of Molecular Sciences","first-page":"1809","article-title":"Oligogenic origin of differences of sex development in humans","volume":"21","author":"Camats","year":"2020","unstructured":"Camats NFl\u00fcck CE & Aud\u00ed L. Oligogenic origin of differences of sex development in humans. International Journal of Molecular Sciences2020211809. (https:\/\/doi.org\/10.3390\/ijms21051809)"},{"key":"bib53","series-title":"Frontiers in Genetics","first-page":"900574","article-title":"Novel genomic variants, atypical phenotypes and evidence of a digenic\/oligogenic contribution to disorders\/differences of sex development in a large North African cohort","volume":"13","author":"Zidoune","year":"2022","unstructured":"Zidoune HLadjouze AChellat-Rezgoune DBoukri ADib SANouri NTebibel MSifi KAbadi NSatta D, Novel genomic variants, atypical phenotypes and evidence of a digenic\/oligogenic contribution to disorders\/differences of sex development in a large North African cohort. Frontiers in Genetics202213900574. (https:\/\/doi.org\/10.3389\/fgene.2022.900574)"},{"key":"bib54","series-title":"Clinical Genetics","first-page":"163","article-title":"Non-coding variation in disorders of sex development","volume":"91","author":"Baetens","year":"2017","unstructured":"Baetens DMendon\u00e7a BBVerdin HCools M & De Baere E. Non-coding variation in disorders of sex development. Clinical Genetics201791163\u2013172. 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