{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:00Z","timestamp":1787021220360,"version":"build-2736575974"},"reference-count":81,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD30428"],"award-info":[{"award-number":["HD30428"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD097096"],"award-info":[{"award-number":["HD097096"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Michigan, MIPM","award":["PICT 2913-2016"],"award-info":[{"award-number":["PICT 2913-2016"]}]},{"name":"University of Michigan, MIPM","award":["PICT 0002-2017"],"award-info":[{"award-number":["PICT 0002-2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted target panel genetic screening using single-molecule molecular inversion probes sequencing to assess the frequency of mutations in known hypopituitarism genes and new candidates in Argentina. We captured genomic deoxyribonucleic acid from 170 pediatric patients with CH, either alone or with other abnormalities. We performed promoter activation assays to test the functional effects of patient variants in LHX3 and LHX4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found variants classified as pathogenic, likely pathogenic, or with uncertain significance in 15.3% of cases. These variants were identified in known CH causative genes (LHX3, LHX4, GLI2, OTX2, HESX1), in less frequently reported genes (FOXA2, BMP4, FGFR1, PROKR2, PNPLA6) and in new candidate genes (BMP2, HMGA2, HNF1A, NKX2-1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this work, we report the prevalence of mutations in known CH genes in Argentina and provide evidence for new candidate genes. We show that CH is a genetically heterogeneous disease with high phenotypic variation and incomplete penetrance, and our results support the need for further gene discovery for CH. Identifying population-specific pathogenic variants will improve the capacity of genetic data to predict eventual clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab177","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:09:51Z","timestamp":1615979391000},"page":"1956-1976","source":"Crossref","is-referenced-by-count":26,"title":["Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders"],"prefix":"10.1210","volume":"106","author":[{"given":"Sebastian Alexis","family":"Vishnopolska","sequence":"first","affiliation":[{"name":"Instituto de Biociencias, Biotecnolog\u00eda y Biolog\u00eda Traslacional (IB3), Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"},{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Florencia","family":"Mercogliano","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Andrea","family":"Camilletti","sequence":"additional","affiliation":[{"name":"Instituto de Biociencias, Biotecnolog\u00eda y Biolog\u00eda Traslacional (IB3), Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"},{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Helen","family":"Mortensen","sequence":"additional","affiliation":[{"name":"Deptartment of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48198-5618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Braslavsky","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1,\u201d (CEDIE), FEI \u2013 CONICET \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Ciudad de Buenos Aires, C1425EFD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Keselman","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1,\u201d (CEDIE), FEI \u2013 CONICET \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Ciudad de Buenos Aires, C1425EFD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Bergad\u00e1","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1,\u201d (CEDIE), FEI \u2013 CONICET \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Ciudad de Buenos Aires, C1425EFD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Marino","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"P\u00e9rez Garrido","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Pati\u00f1o Mejia","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel","family":"Di Palma","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Hospital Garrahan, Ciudad de Buenos Aires, C1245, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-400X","authenticated-orcid":false,"given":"Alicia","family":"Belgorosky","sequence":"additional","affiliation":[{"name":"Hospital de Pediatr\u00eda Garrahan-CONICET, Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Adrian","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica Biolog\u00eda en Exactas y Naturales (IQUIBICEN-CONICET), Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Ciudad de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob Otto","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Deptartment of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48198-5618, 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