{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:34:37Z","timestamp":1772166877476,"version":"3.50.1"},"reference-count":32,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk\u2014characteristic clinical diagnostic findings of PSIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Participants:<\/jats:title>\n                    <jats:p>WES was applied to two affected and one unaffected siblings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein\u2013coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Mutations of GPR161 may be implicated as a potential novel cause of PSIS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2014-1984","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T13:11:10Z","timestamp":1413465070000},"page":"E140-E147","source":"Crossref","is-referenced-by-count":58,"title":["Whole-Exome Sequencing Identifies Homozygous GPR161 Mutation in a Family with Pituitary Stalk Interruption Syndrome"],"prefix":"10.1210","volume":"100","author":[{"given":"Ender","family":"Karaca","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramazan","family":"Buyukkaya","sequence":"additional","affiliation":[{"name":"Department of Radiology (R.B.), Duzce University Medical School, 81620 Duzce, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu-Lin","family":"Charng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kursat O.","family":"Yaykasli","sequence":"additional","affiliation":[{"name":"Department of Medical Biology (K.O.Y.), Kahramanmaras Sutcu Imam University, Medical School, 46100 Kahramanmaras, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yavuz","family":"Bayram","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Withers","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmed M.","family":"Atik","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilknur","family":"Arslanoglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology (I.A., S.B.), Duzce University Medical School, 81620 Duzce, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semih","family":"Bolu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology (I.A., S.B.), Duzce University Medical School, 81620 Duzce, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serkan","family":"Erdin","sequence":"additional","affiliation":[{"name":"Center for Human Genetic Research (S.E.), Massachussetts General Hospital, Boston, Massachussetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayla","family":"Buyukkaya","sequence":"additional","affiliation":[{"name":"Department of Radiology (A.B.), Duzce Ataturk Community Hospital, 81620 Duzce, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emine","family":"Yaykasli","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics (E.Y.), Duzce University Institute of Health Science, 81620 Duzce, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center (S.N.J., D.M.M., R.A.G.), Baylor College of Medicine, Houston Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M.","family":"Muzny","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center (S.N.J., D.M.M., R.A.G.), Baylor College of Medicine, Houston Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"},{"name":"Human Genome Sequencing Center (S.N.J., D.M.M., R.A.G.), Baylor College of Medicine, Houston Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030"},{"name":"Department of Pediatrics (J.R.L.), Baylor College of Medicine, Houston, Texas 77030"},{"name":"Texas Children's Hospital (J.R.L.), Houston, Texas 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071615365764200_B1","doi-asserted-by":"crossref","first-page":"E779","DOI":"10.1210\/jc.2012-3982","article-title":"Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes","volume":"98","author":"Tatsi","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365764200_B2","first-page":"3450","article-title":"Pituitary stalk interruption syndrome: A clinical-biological-genetic assessment of its pathogenesis","volume":"82","author":"Pinto","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365764200_B3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000192447","article-title":"Genetics, gene expression and bioinformatics of the pituitary gland","volume":"71","author":"Davis","year":"2009","journal-title":"Hormone Res"},{"key":"2020071615365764200_B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-416021-7.00001-8","article-title":"Pituitary gland development and disease: From stem cell to hormone production","volume":"106","author":"Davis","year":"2013","journal-title":"Curr Top Dev Biol"},{"key":"2020071615365764200_B5","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1530\/EJE-10-0892","article-title":"Pituitary stalk interruption syndrome in 83 patients: Novel HESX1 mutation and severe hormonal prognosis in malformative forms","volume":"164","author":"Reynaud","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"2020071615365764200_B6","doi-asserted-by":"crossref","first-page":"E1068","DOI":"10.1210\/jc.2011-3056","article-title":"PROKR2 variants in multiple hypopituitarism with pituitary stalk interruption","volume":"97","author":"Reynaud","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615365764200_B7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mce.2009.12.012","article-title":"Molecular mechanisms of pituitary organogenesis: In search of novel regulatory genes","volume":"323","author":"Davis","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"2020071615365764200_B8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/gm415","article-title":"De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome","volume":"5","author":"Bainbridge","year":"2013","journal-title":"Genome Med"},{"key":"2020071615365764200_B9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2105-13-8","article-title":"An integrative variant analysis suite for whole exome next-generation sequencing data","volume":"13","author":"Challis","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2020071615365764200_B10","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2020071615365764200_B11","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":": Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2020071615365764200_B12","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/gim.2011.13","article-title":"NIPBL rearrangements in Cornelia de Lange syndrome: Evidence for replicative mechanism and genotype-phenotype correlation","volume":"14","author":"Pehlivan","year":"2012","journal-title":"Genet Med"},{"key":"2020071615365764200_B13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000181883","article-title":"Hypopituitarism and stalk agenesis: A congenital syndrome worsened by breech delivery?","volume":"35","author":"Maghnie","year":"1991","journal-title":"Hormone Res"},{"key":"2020071615365764200_B14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000207478","article-title":"Role of transcription factors in midline central nervous system and pituitary defects","volume":"14","author":"Kelberman","year":"2009","journal-title":"Endocr Dev"},{"key":"2020071615365764200_B15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1086\/429346","article-title":"Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: Robust phenotype prediction from the type and position of GLI3 mutations","volume":"76","author":"Johnston","year":"2005","journal-title":"Am J Hum Genet"},{"key":"2020071615365764200_B16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1755-8166-7-41","article-title":"Severe growth hormone deficiency and pituitary malformation in a patient with chromosome 2p25 duplication and 2q37 deletion","volume":"7","author":"Vetro","year":"2014","journal-title":"Molecular cytogenetics"},{"key":"2020071615365764200_B17","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmg.2011.03.001","article-title":"17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome","volume":"54","author":"El Chehadeh-Djebbar","year":"2011","journal-title":"Eur J Med Genet"},{"key":"2020071615365764200_B18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/cen.12116","article-title":"Pituitary stalk interruption syndrome in 58 Chinese patients: Clinical features and genetic analysis","volume":"79","author":"Yang","year":"2013","journal-title":"Clin Endocrinol"},{"key":"2020071615365764200_B19","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcp.21257","article-title":"xRic-8 is a GEF for Gsalpha and participates in maintaining meiotic arrest in Xenopus laevis oocytes","volume":"214","author":"Romo","year":"2008","journal-title":"J Cell Physiol"},{"key":"2020071615365764200_B20","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/molehr\/gag097","article-title":"First messenger regulation of capacitation via G protein-coupled mechanisms: A tale of serendipity and discovery","volume":"9","author":"Fraser","year":"2003","journal-title":"Mol Hum Reprod"},{"key":"2020071615365764200_B21","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1083\/jcb.200501104","article-title":"Essential roles of G{alpha}12\/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements","volume":"169","author":"Lin","year":"2005","journal-title":"J Cell Biol"},{"key":"2020071615365764200_B22","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1126\/science.1061259","article-title":"A role for thrombin receptor signaling in endothelial cells during embryonic development","volume":"293","author":"Griffin","year":"2001","journal-title":"Science"},{"key":"2020071615365764200_B23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/35018092","article-title":"A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development","volume":"406","author":"Kupperman","year":"2000","journal-title":"Nature"},{"key":"2020071615365764200_B24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.devcel.2007.01.011","article-title":"Apelin and its receptor control heart field formation during zebrafish gastrulation","volume":"12","author":"Zeng","year":"2007","journal-title":"Dev Cell"},{"key":"2020071615365764200_B25","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1073\/pnas.0705657105","article-title":"The orphan G protein\u2013coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development","volume":"105","author":"Matteson","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020071615365764200_B26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ydbio.2008.08.001","article-title":"The orphan G protein-coupled receptor 161 is required for left-right patterning","volume":"323","author":"Leung","year":"2008","journal-title":"Dev Biol"},{"key":"2020071615365764200_B27","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cell.2012.12.026","article-title":"The ciliary G-protein\u2013coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling","volume":"152","author":"Mukhopadhyay","year":"2013","journal-title":"Cell"},{"key":"2020071615365764200_B28","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1073\/pnas.89.11.5152","article-title":"Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome","volume":"89","author":"Schwindinger","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020071615365764200_B29","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1210\/en.2004-0900","article-title":"Minireview: PRKAR1A: Normal and abnormal functions","volume":"145","author":"Bossis","year":"2004","journal-title":"Endocrinology"},{"key":"2020071615365764200_B30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/35154","article-title":"Regulation of the hedgehog and wingless signalling pathways by the F-box\/WD40-repeat protein Slimb","volume":"391","author":"Jiang","year":"1998","journal-title":"Nature"},{"key":"2020071615365764200_B31","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0092-8674(00)80678-9","article-title":"Hedgehog-regulated processing of Gli3 produces an anterior\/posterior repressor gradient in the developing vertebrate limb","volume":"100","author":"Wang","year":"2000","journal-title":"Cell"},{"key":"2020071615365764200_B32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1534-5807(03)00394-0","article-title":"All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3","volume":"6","author":"Bai","year":"2004","journal-title":"Dev Cell"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/1\/E140\/9096319\/jcemE140.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/1\/E140\/9096319\/jcemE140.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T22:49:02Z","timestamp":1594939742000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/100\/1\/E140\/2812896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2014-1984","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.722182948.793528619","asserted-by":"object"}]},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,1]]}}}