{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:32:49Z","timestamp":1790674369843,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T00:00:00Z","timestamp":1510444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014269","name":"The Philippe Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Koch Institute"},{"name":"The Ludwig Foundation"},{"name":"The Trudy Mandel Louis Charitable Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non\u2010motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11\u2010year\u2010old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy. A homozygous variant, c.870_871del, was identified in the <jats:italic>CDK10<\/jats:italic> gene, predicted to cause a frameshift, p.Trp291Alafs*18, in the cyclin\u2010dependent kinase 10 protein. CDK10 mRNAs were detected in patient cells and do not seem to undergo non\u2010sense mediated decay. CDK10 is the binding partner of Cyclin M (CycM) and CDK10\/CycM protein kinase regulates ciliogenesis and primary cilium elongation. Notably, CycM gene is mutated in patients with STAR syndrome. Following incubation, the patient cells appeared less elongated and more densely populated than the control cells suggesting that the <jats:italic>CDK10<\/jats:italic> mutation affects the cytoskeleton. Upon starvation and staining with acetylated\u2010tubulin, \u03b3\u2010tubulin, and Arl13b, the patient cells exhibited fewer and shorter cilia than control cells. These findings underscore the importance of CDK10 for the regulation of ciliogenesis. CDK10 defect is likely associated with a new form of ciliopathy phenotype; additional patients may further validate this association.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38506","type":"journal-article","created":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T12:42:45Z","timestamp":1510490565000},"page":"92-98","source":"Crossref","is-referenced-by-count":26,"title":["A homozygous deleterious <i>CDK10<\/i> mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness"],"prefix":"10.1002","volume":"176","author":[{"given":"Vincent J.","family":"Guen","sequence":"first","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Edvardson","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"},{"name":"Pediatric Neurology Unit Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitay D.","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Department of Respiratory Rehabilitation Alyn Hospital Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviva","family":"Fattal\u2010Valevski","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Dana\u2010Dwek Children's Hospital Tel Aviv Medical Center and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Jalas","sequence":"additional","affiliation":[{"name":"Bonei Olam Center for Rare Jewish Genetic Disorders Brooklyn New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Anteby","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Shaag","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia","family":"Dor","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gillis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Kerem","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Lees","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Colas","sequence":"additional","affiliation":[{"name":"P<sub>2<\/sub>I<sub>2<\/sub> Group, Protein Phosphorylation and Human Disease Laboratory, Station Biologique de Roscoff Centre National de la Recherche Scientifique and Universit\u00e9 Pierre et Marie Curie Roscoff France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5041-7272","authenticated-orcid":false,"given":"Orly","family":"Elpeleg","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"15006","DOI":"10.1038\/hgv.2015.6","article-title":"The many faces of KIF7","volume":"2","author":"Barakeh D.","year":"2015","journal-title":"Human Genome Variation"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.07.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2512"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.48.28995"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1750-1172-9-74","article-title":"CNS Involvement in OFD1 Syndrome: A Clinical, Molecular, and Neuroimaging Study","volume":"9","author":"Giudice E.","year":"2014","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2774"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.04.024"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306814110"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2016.1147632"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"50174","DOI":"10.18632\/oncotarget.15024","article-title":"The awakening of the CDK10\/Cyclin M protein kinase","volume":"8","author":"Guen V. 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