{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:28:27Z","timestamp":1786368507832,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Great Ormond Street Hospital"},{"DOI":"10.13039\/100012505","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["#535963"],"award-info":[{"award-number":["#535963"]}],"id":[{"id":"10.13039\/100012505","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR GOSH Biomedical Research Center","award":["NIHR-INF-3252"],"award-info":[{"award-number":["NIHR-INF-3252"]}]},{"name":"UCL Excellence Fellowship"},{"name":"GOSH Children's Charity","award":["VS0321"],"award-info":[{"award-number":["VS0321"]}]},{"name":"GOSH Children's Charity","award":["VS2412"],"award-info":[{"award-number":["VS2412"]}]},{"DOI":"10.13039\/100032590","name":"Stoneygate Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["UCL2021\/1"],"award-info":[{"award-number":["UCL2021\/1"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UKRI MRC New Investigator Research","award":["MR\/X003957\/1"],"award-info":[{"award-number":["MR\/X003957\/1"]}]},{"DOI":"10.13039\/501100019256","name":"NIHR GOSH BRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030827","name":"NHS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004856","name":"Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective &amp; Design<\/jats:title>\n                    <jats:p>Congenital Hypopituitarism (CH) is a complex developmental disorder characterized by variable pituitary dysfunction that is often associated with midline structural abnormalities that affect the brain, eyes and face. To date, only \u223c10%-15% of patients have an underlying molecular basis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Next generation sequencing was conducted on a subset of CH patients with no known genetic aetiology. Human embryonic brain tissue sections were used to generate an expression profile, and a knock-out mouse model was generated using CRISPR-Cas9 gene editing and phenotypically analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two novel homozygous frameshifts in CCDC149, p.Gly278* and p.Leu222*, were identified in two unrelated CH pedigrees (three patients), respectively. Patient phenotypes included growth hormone deficiency (GHD), hypogonadotropic hypogonadism, and developmental delay\/autism. Severe scoliosis was present in one pedigree, with a small anterior pituitary on MRI in the other. Human embryonic CCDC149 was localized to the developing hypothalamo-pituitary region at Carnegie stages 16-23, and Ccdc149-null mice recapitulated patient phenotypes, including growth impairment and reduced fertility compared with wild-type littermates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study is the first to report CCDC149 variants in association with CH. Previous studies in C.elegans report CCDC149 orthologue expression in the basal bodies of ciliated neurons, supporting the possibility of impaired ciliary function as an underlying mechanism in this complex disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag140","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:37:43Z","timestamp":1785843463000},"page":"237-249","source":"Crossref","is-referenced-by-count":0,"title":["<i>CCDC149<\/i>\n                    : a novel gene associated with hypopituitarism and neurodevelopmental impairment"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7463-5365","authenticated-orcid":false,"given":"Louise C","family":"Gregory","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health , London WC1N 1EH ,","place":["United 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