{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:26Z","timestamp":1784557046118,"version":"3.55.0"},"reference-count":15,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (\n                      <jats:italic>NR5A1<\/jats:italic>\n                      ), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the\n                      <jats:italic>NR5A1<\/jats:italic>\n                      gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the\n                      <jats:italic>NR5A1<\/jats:italic>\n                      gene. A retrospective evaluation of the medical history, physical examination, limited endocrinological laboratory analysis and genetic analysis with DSD gene panel testing was performed. A 1.5-month-old individual was referred with ambiguous genitalia. The karyotype was 46,XY. The endocrinological analyses were within normal male reference including a normal response of cortisol within an adrenocorticotropic hormone test. A novel heterozygous missense variant c.206G&gt;C p.(Arg69Pro) in the\n                      <jats:italic>NR5A1<\/jats:italic>\n                      gene was detected. This variant was present in mosaic form (~20%) in his unaffected father. Because another missense variant at the same position and other missense variants involving the same highly conserved codon have been reported, we consider this\n                      <jats:italic>NR5A1<\/jats:italic>\n                      variant in this 46,XY DSD patient as likely pathogenic in accordance with the ACMG\/AMP 2015 guidelines causing ambiguous genitalia but no adrenal insufficiency. This variant was inherited from the apparently unaffected mosaic father, which might have implications for the recurrence risk in this family.\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>The importance of performing trio (patient and parents) sequencing is crucial in pointing out the origin of inheritance.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          In a 46,XY differences of sex development patient, a normal adrenal function does not rule out an\n                          <jats:italic>NR5A1<\/jats:italic>\n                          mutation.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>With the support of a dedicated overseas institute partnership, we could solve this complex clinical case by molecular diagnosis in a resource-limited setting.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-22-0384","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T13:32:43Z","timestamp":1682515963000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["Novel likely pathogenic variant in NR5A1 gene in a Tanzanian child with 46,XY differences of sex development, inherited from the mosaic father"],"prefix":"10.1530","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-4804","authenticated-orcid":true,"given":"Rahim Karim","family":"Damji","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Regency Medical Centre, Dar es Salaam, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Zahir","family":"Alimohamed","sequence":"additional","affiliation":[{"name":"Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania"},{"name":"Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania"},{"name":"Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Tanzania Human Genetics Organization, Dar es Salaam, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedi L","family":"Claahsen-van der Grinten","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Amalia Children\u2019s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dineke","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Hamel","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","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. 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