{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:01Z","timestamp":1784557021309,"version":"3.55.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5]]},"abstract":"\n Aim<\/jats:title>\n Congenital hypopituitarism has an incidence of 1:3500\u201310,000 births and is defined by the impaired production of pituitary hormones. Early diagnosis has an impact on management and genetic counselling. The clinical and genetic heterogeneity of hypopituitarism poses difficulties to select the order of genes to analyse. The objective of our study is to screen hypopituitarism genes (candidate and previously related genes) simultaneously using a target gene panel in patients with congenital hypopituitarism.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Screening of 117 subjects with congenital hypopituitarism for pathogenic variants in 26 genes associated with congenital hypopituitarism by massively parallel sequencing using a customized target gene panel.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found three novel pathogenic variants in\n OTX2<\/jats:italic>\n c.295C>T:p.Gln99*,\n GLI2<\/jats:italic>\n c.1681G>T:p.Glu561* and\n GHRHR<\/jats:italic>\n c.820_821insC:p.Asp274Alafs*113, and the previously reported variants in\n GHRHR<\/jats:italic>\n c.57+1G>A and\n PROP1<\/jats:italic>\n [c.301_302delAG];[c.109+1G>A].\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results indicate that a custom-designed panel is an efficient method to screen simultaneously variants of biological and clinical relevance for congenital GH deficiency. A genetic diagnosis was possible in 5 out of 117 (4%) patients of our cohort. We identified three novel pathogenic variants in\n GHRHR<\/jats:italic>\n ,\n OTX2<\/jats:italic>\n and\n GLI2<\/jats:italic>\n expanding the spectrum of variants associated with congenital hypopituitarism.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/ec-19-0085","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:26:07Z","timestamp":1554377167000},"page":"590-595","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":8,"title":["Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR"],"prefix":"10.1530","volume":"8","author":[{"given":"Marilena","family":"Nakaguma","sequence":"first","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda A","family":"Correa","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S","family":"Santana","sequence":"additional","affiliation":[{"name":"2Unidade de Endocrinologia Gen\u00e9tica, Laborat\u00f3rio de Endocrinologia Celular e Molecular LIM25, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna F F","family":"Benedetti","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo V","family":"Perez","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de Endocrinologia, Hospital do Servidor P\u00fablico Estadual de S\u00e3o Paulo, Instituto de Assist\u00eancia M\u00e9dica ao Servidor P\u00fablico Estadual (HSPE-IAMSPE), S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha K P","family":"Huayllas","sequence":"additional","affiliation":[{"name":"4Hospital de Transplantes Euryclides de Jesus Zerbini, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirta B","family":"Miras","sequence":"additional","affiliation":[{"name":"5Hospital de Ni\u00f1os Sant\u00edsima Trinidad, Cordoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana F A","family":"Funari","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio M","family":"Lerario","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciani R S","family":"Carvalho","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A L","family":"Jorge","sequence":"additional","affiliation":[{"name":"2Unidade de Endocrinologia Gen\u00e9tica, Laborat\u00f3rio de Endocrinologia Celular e Molecular LIM25, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo J P","family":"Arnhold","sequence":"additional","affiliation":[{"name":"1Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Disciplina de Endocrinologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref121","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/cen.13914","article-title":"Novel GLI2 mutations identified in patients with Combined Pituitary Hormone Deficiency (CPHD): evidence for a pathogenic effect by functional characterization","volume":"90","year":"2019","journal-title":"Clinical Endocrinology"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1210\/jc.2008-2783","article-title":"Expanding the spectrum of mutations in GH1 and GHRHR: genetic 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