{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:41:19Z","timestamp":1772253679087,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:sec>\n<jats:title>Context<\/jats:title>\n<jats:p>Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Retrospective study.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by <jats:italic>in silico<\/jats:italic> prediction tools. The correlation between clinical and genotype diagnosis was analysed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0387","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T17:55:46Z","timestamp":1629222946000},"page":"617-627","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":23,"title":["Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-504X","authenticated-orcid":true,"given":"Tansit","family":"Saengkaew","sequence":"first","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"2Endocrinology Unit, Department of Paediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heena R","family":"Patel","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"3Department of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norfolk, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kausik","family":"Banerjee","sequence":"additional","affiliation":[{"name":"4Department of Paediatrics, Barking, Havering and Redbridge University Hospitals NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Butler","sequence":"additional","affiliation":[{"name":"5Department of Paediatric and Adolescent Endocrinology, University College London Hospital NHS Foundation Trust, London, UK"},{"name":"6UCL Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehul T","family":"Dattani","sequence":"additional","affiliation":[{"name":"5Department of Paediatric and Adolescent Endocrinology, University College London Hospital NHS Foundation Trust, London, UK"},{"name":"6UCL Great Ormond Street Institute of Child Health, University College London, London, UK"},{"name":"7Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"McGuigan","sequence":"additional","affiliation":[{"name":"8Department of Paediatrics, Countess of Chester NHS Foundation Trust, Chester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen L","family":"Storr","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"9Department of Paediatric Endocrinology, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben H","family":"Willemsen","sequence":"additional","affiliation":[{"name":"9Department of Paediatric Endocrinology, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Dunkel","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"9Department of Paediatric Endocrinology, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-903X","authenticated-orcid":true,"given":"Sasha R","family":"Howard","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"9Department of Paediatric Endocrinology, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/5\/EJE-21-0387.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/5\/EJE-21-0387.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:42Z","timestamp":1676391402000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/5\/617\/6654382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":0,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0387","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}