{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:21:22Z","timestamp":1792131682853,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T00:00:00Z","timestamp":1508457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea\/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including <jats:italic>INPP5E<\/jats:italic>, a gene encoding inositol polyphosphate 5\u2010phosphatase E, which is important in the development and stability of the primary cilium. Here, we report the detailed clinical phenotypes of two sisters with a novel homozygous variant in <jats:italic>INPP5E<\/jats:italic> (NM_019892.4: c.1565G&gt;C, NP_063945.2: p.Gly552Ala), expanding the phenotype associated with Joubert syndrome type 1. Expression studies using patient\u2010derived fibroblasts showed changes in mRNA and protein levels. Analysis of fibroblasts from patients revealed that a significant number of cells had shorter or no cilia, indicating defects in ciliogenesis, and cilia maintenance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38376","type":"journal-article","created":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T08:22:41Z","timestamp":1508487761000},"page":"3231-3237","source":"Crossref","is-referenced-by-count":25,"title":["Defective ciliogenesis in <i>INPP5E\u2010<\/i>related Joubert syndrome"],"prefix":"10.1002","volume":"173","author":[{"given":"Isabel","family":"Hardee","sequence":"first","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Soldatos","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National 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Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"David","sequence":"additional","affiliation":[{"name":"New York Methodist Hospital Brooklyn New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-1046","authenticated-orcid":false,"given":"Carlos R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Nehrebecky","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Snow","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, National Institute of Mental health National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Thurm","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, National Institute of Mental health National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Heller","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen F.","family":"Macnamara","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Office of the Clinical Director, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral","family":"Gunay\u2010Aygun","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Office of the Clinical Director, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Department of Pediatrics and McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih M.","family":"Zein","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch, National Eye Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Office of the Clinical Director, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-6959","authenticated-orcid":false,"given":"May Christine V.","family":"Malicdan","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"},{"name":"Medical Genetics Branch, National Human Genome Research Institute National 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