{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:50:17Z","timestamp":1781938217016,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":169,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD108156"],"award-info":[{"award-number":["R01HD108156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    PNPLA6 is a conserved lysophospholipase essential for maintaining nervous system integrity. Biallelic mutations in\n                    <jats:italic>PNPLA6<\/jats:italic>\n                    have been identified in individuals with a broad spectrum of disorders that can include ataxia, vision loss, and pituitary hormone deficiency. Here, we report the identification of novel compound heterozygous variants in\n                    <jats:italic>PNPLA6<\/jats:italic>\n                    (p.T1115P and p.Pro1142_Ala1143ins14) in a 10\u2010year\u2010old girl with combined pituitary hormone deficiency, including growth hormone, thyroid\u2010stimulating hormone, and gonadotropins. She also has vision loss and neurodevelopmental delay. Functional validation demonstrates that both variants, a missense substitution affecting a highly conserved residue within the catalytic domain and an intronic variant generating a novel splice acceptor site, completely abolish NTE activity, establishing their pathogenicity. Little is known about the cause of hypopituitarism in individuals with\n                    <jats:italic>PNPLA6<\/jats:italic>\n                    deficiency. Here, we report the cell\u2010type\u2010specific expression of PNPLA6 in mouse pituitary development and in adult animals. PNPLA6 is expressed broadly in SOX2+ stem cells within the pituitary primordium as early as e10.5, prior to lineage specification, suggesting a role in progenitor maintenance and early differentiation. In neonates and adults, expression predominates in the cells that produce growth hormone and pro\u2010opiomelanocortin. These findings suggest that PNPLA6 could influence pituitary development at early stages, as well as contribute to the altered function of hormone\u2010secreting cells.\n                  <\/jats:p>","DOI":"10.1155\/humu\/4515038","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:59:01Z","timestamp":1781935141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compound Heterozygous Variants in the Phospholipase Gene PNPLA6 Cause Hypopituitarism and Vision Loss"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-9948","authenticated-orcid":false,"given":"Sebastian","family":"Vishnopolska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2871-3865","authenticated-orcid":false,"given":"James","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-5523","authenticated-orcid":false,"given":"Maria Andrea","family":"Camilletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-7291","authenticated-orcid":false,"given":"Julian Martinez","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1186-7692","authenticated-orcid":false,"given":"Lucia Iglesias","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-4682","authenticated-orcid":false,"given":"Michelle","family":"Brinkmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-8120","authenticated-orcid":false,"given":"Elisa","family":"Vaiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0568-2947","authenticated-orcid":false,"given":"Sofia Hebe","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-0713","authenticated-orcid":false,"given":"Marta","family":"Ciaccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Di Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-400X","authenticated-orcid":false,"given":"Alicia","family":"Belgorosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-9340","authenticated-orcid":false,"given":"Marcelo","family":"Marti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-3379","authenticated-orcid":false,"given":"Sally A.","family":"Camper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-109X","authenticated-orcid":false,"given":"Maria Ines","family":"Perez-Millan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_2_13_1_2","first-page":"1738","article-title":"PNPLA6 Mutations Cause Oliver-Mcfarlane Syndrome","volume":"167","author":"Hufnagel R. B.","year":"2015","journal-title":"American Journal of Medical Genetics Part A"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt326"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae055"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102856"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001521"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01207"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57402-8"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae320"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab177"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_13_11_2","volume-title":"Genomics in the Cloud","author":"van der Auwera G.","year":"2020"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae410"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2025.106768"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00293860"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/15.2.86"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.10.048"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199306000-00050"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2012-0505"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad472"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1836"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100881"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/4515038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/4515038","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/4515038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:59:03Z","timestamp":1781935143000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/4515038"}},"subtitle":[],"editor":[{"given":"Elfride","family":"De Baere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/4515038"],"URL":"https:\/\/doi.org\/10.1155\/humu\/4515038","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"4515038"}}