{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:01Z","timestamp":1784557021528,"version":"3.55.0"},"reference-count":11,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      Delayed puberty in girls is often related to late maturation but is occasionally the first sign of premature ovarian insufficiency (POI). POI is a condition that affects ovarian function and fertility, and its etiology is unknown in most cases. Genetic factors have recently been identified in 20\u201325% of women with POI, involving genes that regulate various aspects of ovarian development and maintenance. We report a case of delayed puberty due to POI in an adolescent from a non-consanguineous family who carried two variants in the\n                      <jats:italic>MCM9<\/jats:italic>\n                      gene. MCM9 is essential for DNA replication and repair, and its dysfunction can lead to chromosomal instability and ovarian failure. Our case highlights the importance of targeted gene panel analysis, particularly in POI patients with negative autoimmunity screening, and evidence of ovarian or uterine dysgenesis on pelvic imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Delayed puberty in girls is often self-limiting, but it can also indicate underlying conditions with lifelong implications, such as premature ovarian insufficiency (POI).<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Patients with POI, negative autoimmune screening, a normal karyotype, and no FMR premutation should undergo further genetic testing, preferably through targeted gene panels.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Compound heterozygous variants in\n                          <jats:italic>MCM9<\/jats:italic>\n                          can cause POI, presenting with delayed puberty and primary amenorrhea in girls without a consanguineous family.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-24-0012","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T07:41:56Z","timestamp":1729755716000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["MCM9 compound heterozygosity in an adolescent with premature ovarian insufficiency"],"prefix":"10.1530","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-9126","authenticated-orcid":true,"given":"Elise","family":"Nauwynck","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Growth & Development (GRON), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-5924","authenticated-orcid":true,"given":"Michel","family":"De Vos","sequence":"additional","affiliation":[{"name":"Brussels IVF, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Clinical Sciences, Research Group Reproduction and Genetics, Centre for Medical Genetics, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-1961","authenticated-orcid":true,"given":"Alexander","family":"Gheldof","sequence":"additional","affiliation":[{"name":"Division of Genetics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart JH","family":"Dequeker","sequence":"additional","affiliation":[{"name":"Division of Genetics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-1960","authenticated-orcid":true,"given":"Annelore","family":"Van Der Kelen","sequence":"additional","affiliation":[{"name":"Division of Genetics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3025-0882","authenticated-orcid":true,"given":"Frederik","family":"Hes","sequence":"additional","affiliation":[{"name":"Clinical Sciences, Research Group Reproduction and Genetics, Centre for Medical Genetics, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"},{"name":"Division of Genetics, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Verheyden","sequence":"additional","affiliation":[{"name":"Pediatrics, OLV Aalst Campus Asse, Asse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-6139","authenticated-orcid":true,"given":"Jesse","family":"Vanbesien","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Growth & Development (GRON), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-0858","authenticated-orcid":true,"given":"Inge","family":"Gies","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Growth & Development (GRON), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-0250","authenticated-orcid":true,"given":"Jean","family":"De Schepper","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Growth & Development (GRON), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3329","authenticated-orcid":true,"given":"Willem","family":"Staels","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Genetics, Reproduction, and Development (GRAD), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Seminars in Reproductive Medicine","first-page":"3","article-title":"Disorders of puberty in girls","volume":"40","author":"Sopher","year":"2022","unstructured":"Sopher ABOberfield SE & Witchel SF. 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Molecular genetics of premature ovarian insufficiency. Trends in Endocrinology and Metabolism 2018 29 795\u2013807. (https:\/\/doi.org\/10.1016\/j.tem.2018.07.002)"},{"key":"bib4","series-title":"PLoS One","first-page":"e0240795","article-title":"Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency","volume":"15","author":"Franca","year":"2020","unstructured":"Franca MMFunari MFALerario AMSantos MGNishi MYDomenice SMoraes DRCostalonga EFMaciel GARMaciel-Guerra AT, et al. Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency. PLoS One 2020 15 e0240795. 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DNA Repair 2019 76 1\u201310. (https:\/\/doi.org\/10.1016\/j.dnarep.2019.02.003)"},{"key":"bib11","series-title":"Molecular Cell","first-page":"523","article-title":"MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination","volume":"47","author":"Lutzmann","year":"2012","unstructured":"Lutzmann MGrey CTraver SGanier OMaya-Mendoza ARanisavljevic NBernex FNishiyama AMontel NGavois E, et al. MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination. Molecular Cell 2012 47 523\u2013534. 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