{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:35:46Z","timestamp":1793424946025,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Steroidogenic factor 1 (SF1,\n                      <jats:italic>NR5A1<\/jats:italic>\n                      ) is a key transcriptional regulator of genes involved in the hypothalamic\u2013pituitary\u2013gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of\n                      <jats:italic>NR5A1<\/jats:italic>\n                      mutations in an Egyptian cohort of XY DSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Clinical assessment, endocrine evaluation and genetic analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a wide phenotypic spectrum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Molecular analysis of\n                      <jats:italic>NR5A1<\/jats:italic>\n                      gene by direct sequencing followed by\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional analysis of the two novel missense mutations detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three novel heterozygous mutations of the coding region in patients with hypospadias were detected. p.Glu121AlafsX25 results in severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using reporter constructs carrying promoters of anti-M\u00fcllerian hormone (\n                      <jats:italic>AMH<\/jats:italic>\n                      ),\n                      <jats:italic>CYP11A1<\/jats:italic>\n                      and TESCO core enhancer of\n                      <jats:italic>Sox9<\/jats:italic>\n                      showed that p.Ala154Thr and p.Arg62Cys mutations result in aberrant biological activity of\n                      <jats:italic>NR5A1<\/jats:italic>\n                      . A total of 17 patients (34%) harboured the p.Gly146Ala polymorphism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We identified two novel\n                      <jats:italic>NR5A1<\/jats:italic>\n                      mutations showing impaired function in 23 Egyptian XY DSD patients with hypospadias (8.5%). This is the first study searching for\n                      <jats:italic>NR5A1<\/jats:italic>\n                      mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5\u201315%). We recommend screening of\n                      <jats:italic>NR5A1<\/jats:italic>\n                      in patients with hypospadias and gonadal dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of sperms should be performed in XY DSD patients with\n                      <jats:italic>NR5A1<\/jats:italic>\n                      mutations given the risk of future fertility problems due to early gonadal failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-13-0965","type":"journal-article","created":{"date-parts":[[2014,3,4]],"date-time":"2014-03-04T00:34:16Z","timestamp":1393893256000},"page":"759-767","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":36,"title":["Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex 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