{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:03:47Z","timestamp":1783595027877,"version":"3.55.0"},"reference-count":14,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"name":"Ministry of Health, Labor and Welfare of Japan Research on Rare and Intractable Diseases","award":["28-Ippan-010"],"award-info":[{"award-number":["28-Ippan-010"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan Research on Rare and Intractable Diseases","award":["28-Ippan-010"],"award-info":[{"award-number":["28-Ippan-010"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["16ek0109145h0002"],"award-info":[{"award-number":["16ek0109145h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["17ek0109145h0003"],"award-info":[{"award-number":["17ek0109145h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Joubert syndrome (JS) is a genetic neurodevelopmental disorder characterized by lower brainstem dysplasia and cerebellar vermis agenesis termed molar tooth sign (MTS), psychomotor retardation, abnormal respiratory pattern in infancy, and oculomotor abnormalities. Arima syndrome (AS), which is a severe form of JS, is characterized by severe psychomotor retardation, congenital visual impairment, progressive renal dysfunction, and lower brainstem dysplasia from early infancy. Numerous patients with AS expire in early childhood. Recently, c.6012\u201312T&gt; A in the CEP290 gene was reported as a specific variant of AS. Herein, we report the cases of two siblings showing a phenotype of JS with compound heterozygous mutations (c.6012\u201312T\u2009&gt;\u2009A \/ c.5924delT) in the CEP290 gene. The older sister (aged 19 years) had hypotonia, hypertelorism, and anteverted nares since birth. As a neonate, she developed a transient abnormal respiratory pattern and nystagmus, and brain magnetic resonance imaging (MRI) showed MTS. The younger sister (aged 13 years) exhibited mild hypotonia and pendular nystagmus as a neonate; MRI revealed MTS. Both sisters had psychomotor retardation, oculomotor dysfunction, and bilateral renal cysts with normal renal function. They can walk and have simple conversation. They do not meet the diagnostic criteria for AS, and their symptoms were milder than those of previously reported cases with this specific mutation. This report indicates the expanding spectrum of the CEP290 variant.<\/jats:p>","DOI":"10.1055\/a-1865-6890","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T06:27:57Z","timestamp":1654064877000},"page":"217-221","source":"Crossref","is-referenced-by-count":3,"title":["Two Siblings Showing a Mild Phenotype of Joubert Syndrome with a Specific CEP290 Variant"],"prefix":"10.1055","volume":"54","author":[{"given":"Daisuke","family":"Uda","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tanda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenro","family":"Kizaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,8,28]]},"reference":[{"issue":"09","key":"ref1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1212\/WNL.19.9.813","article-title":"Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation","volume":"19","author":"M Joubert","year":"1969","journal-title":"Neurology"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1177\/088307389901400605","article-title":"Molar tooth sign in Joubert syndrome: clinical, radiologic, and pathologic significance","volume":"14","author":"B L Maria","year":"1999","journal-title":"J Child Neurol"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ajmg.a.20437","article-title":"Molar tooth sign of the midbrain-hindbrain junction: occurrence in multiple distinct syndromes","volume":"125A","author":"J G Gleeson","year":"2004","journal-title":"Am J Med Genet A"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.braindev.2017.11.002","article-title":"Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases","volume":"40","author":"M Itoh","year":"2018","journal-title":"Brain Dev"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.braindev.2013.06.005","article-title":"Nationwide survey of Arima syndrome: revised diagnostic criteria from epidemiological analysis","volume":"36","author":"M Itoh","year":"2014","journal-title":"Brain Dev"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/ajmg.a.30294","article-title":"Renal disease in Arima syndrome is nephronophthisis as in other Joubert-related Cerebello-oculo-renal syndromes","volume":"131","author":"S Kumada","year":"2004","journal-title":"Am J Med Genet A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1750-1172-5-20","article-title":"Joubert syndrome and related disorders","volume":"5","author":"F Brancati","year":"2010","journal-title":"Orphanet J Rare Dis"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.3390\/genes11111240","article-title":"A mild phenotype caused by two novel compound heterozygous mutations in CEP290","volume":"11","author":"A Rafalska","year":"2020","journal-title":"Genes (Basel)"},{"issue":"06","key":"ref10","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/cge.12836","article-title":"Molecular genetic analysis of 30 families with Joubert syndrome","volume":"90","author":"T Suzuki","year":"2016","journal-title":"Clin Genet"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1086\/519026","article-title":"CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders","volume":"81","author":"F Brancati","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/jum.15435","article-title":"Ultrasound imaging of renal cysts in children","volume":"40","author":"C C Thomas","year":"2021","journal-title":"J Ultrasound Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","article-title":"Autosomal dominant polycystic kidney disease","volume":"393","author":"E Cornec-Le Gall","year":"2019","journal-title":"Lancet"},{"issue":"10","key":"ref14","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/humu.21337","article-title":"CEP290, a gene with many faces: mutation overview and presentation of CEP290base","volume":"31","author":"F Coppieters","year":"2010","journal-title":"Hum Mutat"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1055\/s-2007-973701","article-title":"Follow-up in children with Joubert syndrome","volume":"28","author":"M Steinlin","year":"1997","journal-title":"Neuropediatrics"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1865-6890.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:13:04Z","timestamp":1683591184000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1865-6890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":14,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2023,5,8]]},"published-print":{"date-parts":[[2023,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1865-6890","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,31]]},"published":{"date-parts":[[2022,5,31]]}}}