{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:46:52Z","timestamp":1791172012368,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>WFS1<\/jats:italic>\n                      spectrum disorder, also known as Wolfram syndrome (WS) is an ultra\u2010rare (&lt;1:500,000; ORPHA: 3463) monogenic (OMIM #222300) progressive neuroendocrine and neurodegenerative disorder, characterised by early\u2010onset insulin\u2010dependent diabetes, optic atrophy, central diabetes insipidus and sensi\u2010neuronal deafness. It is caused predominantly by bi\u2010allelic mutations in the\n                      <jats:italic>WFS1<\/jats:italic>\n                      gene and exceptionally in the\n                      <jats:italic>WFS2<\/jats:italic>\n                      \u2010gene. There is very limited published data on gonadal function in young people with WS. Expansion of the phenotype has previously included suggestions of abnormalities in puberty in adolescents with (WS) but with little detail.\n                      <jats:sup>1\u20133<\/jats:sup>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To assess testicular function and pubertal progression in a cohort of adolescent and young adult patients with classical\n                      <jats:italic>WFS1<\/jats:italic>\n                      spectrum disorder (WS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective case notes review of national patient cohorts comprising 21 males with WS aged 16\u201330 years. All patients were treated in two tertiary European health care centres: in Birmingham, UK and M\u00fcnster, Germany. Hormonal parameters reflecting hypothalamic\u2013pituitary\u2013gonadal axis function and treatment with sex hormones were assessed. In addition, the presence or absence of erectile dysfunction was explored. In a subset of men, semen data were analysed. In one young man, testicular biopsies were examined histologically using light and electron microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Severely delayed or arrested puberty was observed in 57% of male adolescents with WS, necessitating testosterone replacement for completion of pubertal development.<\/jats:p>\n                    <jats:p>\n                      Subclinical (compensated) hypergonadotropic hypogonadism with still adequate testosterone serum concentration for age, but elevated LH\/FSH was observed in 28.6% (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06). In two males, aged 19 and 16 years (9.5%), inadequately low LH\/FSH and testosterone levels indicated hypogonadotropic hypogonadism.\n                    <\/jats:p>\n                    <jats:p>In the subset of males with normal puberty and normal endocrine testicular function (43% of male patients), the oldest, aged 30 years had normal sperm count in semen. Another young man had oligozoospermia at age 20, but azoospermia at age 25 years. Histology of his testicular tissues evidenced structural alterations of Leydig and Sertoli cells and tubular atrophy with various stages of tubular degeneration and meiotic arrest of spermatogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Endocrine testicular function and reproductive capacity are impaired in males with WS potentially due to premature degeneration of the testes, with 57% of adolescents developing hypogonadism with pubertal arrest.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70049","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T05:05:40Z","timestamp":1745903140000},"page":"398-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gonadal function in males with WFS1 spectrum disorder (Wolfram syndrome)\u2014A European cohort perspective"],"prefix":"10.1111","volume":"14","author":[{"given":"Julia","family":"Rohayem","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes Children's Hospital of Eastern Switzerland  St. Gallen Switzerland"},{"name":"Centre for Reproductive Medicine and Andrology University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Birmingham Women's Hospital Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Wistuba","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Regenerative Biology Centre of Reproductive Medicine and Andrology, University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Paediatric Urology Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"},{"name":"Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5743-1077","authenticated-orcid":false,"given":"Renuka P.","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"},{"name":"Institute of Applied Health Research, College of Medical and Dental Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10\u20101937"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010018\u20101608\u20102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1155644"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0025-6196(26)04711-7","article-title":"Diabetes mellitus and simple optic atrophy among siblings: report on four cases","volume":"13","author":"Wolfram DJ","year":"1938","journal-title":"Mayo Clin Proc"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(95)92473\u20106"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/2441"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.09.007"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu499"},{"key":"e_1_2_10_10_1","unstructured":"BarrettT Tranebj\u00e6rgL GuptaR.WFS1 Spectrum Disorder. 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