{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:15:04Z","timestamp":1761848104060,"version":"build-2065373602"},"reference-count":45,"publisher":"Walter de Gruyter GmbH","issue":"11","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018996","name":"Hellenic Academic Libraries Link","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0086_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The majority of congenital hypopituitarism (CH) cases remain genetically unexplained. The transmembrane receptor Roundabout-1 (\n                      <jats:italic>ROBO1<\/jats:italic>\n                      ), activated through interaction with SLIT-family proteins, plays crucial role in axonal guidance, branching, targeting, and midline axonal crossing.\n                      <jats:italic>ROBO1<\/jats:italic>\n                      variants have been associated with pituitary stalk interruption syndrome and highly variable pituitary-phenotypes, ranging from isolated growth hormone deficiency (IGHD) to combined pituitary hormone deficiency (CPHD). This study aimed to investigate the genetic basis of CH in a newborn and to review current evidence linking\n                      <jats:italic>ROBO1<\/jats:italic>\n                      variants with\u00a0CH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0086_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report the presence of two\n                      <jats:italic>ROBO1<\/jats:italic>\n                      \u00a0variants in compound heterozygosity, the NM_002941:c.2914G&gt;A, p.(Ala972Thr) and the novel NM_002941:c.3757G&gt;A, p.(Val1253Met), as well as the identification of the novel\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variant NM_000435:c.1505C&gt;T, p.(Ser502Phe) and the novel\n                      <jats:italic>GPR161<\/jats:italic>\n                      variant NM_001375883.1:c.1117C&gt;T, p.(His373Tyr), in a newborn with CPHD, dysmorphic features and midline abnormalities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0086_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case, together with accumulating evidence, supports\n                      <jats:italic>ROBO1<\/jats:italic>\n                      as a potential causative gene for CH.\n                      <jats:italic>ROBO1<\/jats:italic>\n                      should be considered during genetic evaluation of patients with CH and midline abnormalities. The co-occurrence of\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      and\n                      <jats:italic>GPR161<\/jats:italic>\n                      variants raises the possibility of an oligogenic or multigenic etiology. The cross-talk between ROBO\/SLIT and NOTCH signaling pathways may contribute to the complex phenotype observed and warrants further functional investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0086","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T08:55:48Z","timestamp":1756544148000},"page":"1224-1236","source":"Crossref","is-referenced-by-count":0,"title":["Compound heterozygous\n                    <i>ROBO1<\/i>\n                    gene variants in a neonate with congenital hypopituitarism, dysmorphic features and midline abnormalities: a case report and review of the literature"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3284-4465","authenticated-orcid":false,"given":"Panagiota","family":"Markopoulou","sequence":"first","affiliation":[{"name":"Neonatology Unit, First Department of Pediatrics, Medical School , National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"Sertedaki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School , 68993 National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Nikaina","sequence":"additional","affiliation":[{"name":"Neonatology Unit, First Department of Pediatrics, Medical School , National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Binou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School , 68993 National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioanna","family":"Farakla","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School , 68993 National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Siahanidou","sequence":"additional","affiliation":[{"name":"Neonatology Unit, First Department of Pediatrics, Medical School , National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Kanaka-Gantenbein","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School , 68993 National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"2025103018011135688_j_jpem-2025-0086_ref_001","doi-asserted-by":"crossref","unstructured":"Davis, SW, Ellsworth, BS, Per\u00e9z Millan, MI, Gergics, P, Schade, V, Foyouzi, N, et al.. 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