{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:29:56Z","timestamp":1772166596156,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012470","name":"Doctoral Program Foundation of Institutions of Higher Education of China","doi-asserted-by":"publisher","award":["2018M640920"],"award-info":[{"award-number":["2018M640920"]}],"id":[{"id":"10.13039\/501100012470","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Project of Science and Technology Bureau of Chengdu","award":["2016-HM01-00257-SF"],"award-info":[{"award-number":["2016-HM01-00257-SF"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Joubert syndrome (JS) is a rare genetic disorder, which can be defined by brain stem malformation, cerebellar vermis hypoplasia, and consequent \u201cmolar tooth sign\u201d (MTS). JS always shares variety of phenotypes in development defects. With the development of next-generation sequencing, dozens of causative genes have been identified to JS so far. Here, we investigated two male siblings with JS and uncovered a novel pathogenesis through combined methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The siblings shared similar features of nystagmus, disorders of intellectual development, typical MTS, and abnormal morphology in fourth ventricle. Whole-exome sequencing (WES) and chromosome comparative genomic hybridization (CGH) were then performed on the proband. Strikingly, a maternal inherited nonsense variant (NM_025114.3: c.5953G&gt;T [p.E1985*]) in\n                      <jats:italic>CEP290<\/jats:italic>\n                      gene and a paternal inherited deletion in 12q21.32 including exons 1 to 10 of\n                      <jats:italic>CEP290<\/jats:italic>\n                      gene were identified in the two affected siblings. We further confirmed the two variants by in vitro experiments: quantitative PCR and PCR sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this study, we first reported a novel causative mechanism of Joubert syndrome: a copy number variation (CNV) combined with a single-nucleotide variant in\n                      <jats:italic>CEP290<\/jats:italic>\n                      gene, which can be helpful in the genetic diagnosis of this disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-020-00274-4","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T08:04:05Z","timestamp":1593417845000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel biallelic loss-of-function variants in CEP290 cause Joubert syndrome in two siblings"],"prefix":"10.1186","volume":"14","author":[{"given":"Xiang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5229-793X","authenticated-orcid":false,"given":"Hongqian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"issue":"9","key":"274_CR1","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1212\/WNL.19.9.813","volume":"19","author":"M Joubert","year":"1969","unstructured":"Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969;19(9):813\u201325.","journal-title":"Neurology."},{"issue":"1","key":"274_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1055\/s-0028-1091505","volume":"8","author":"E Boltshauser","year":"1977","unstructured":"Boltshauser E, Isler W. Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. Neuropadiatrie. 1977;8(1):57\u201366.","journal-title":"Neuropadiatrie."},{"key":"274_CR3","doi-asserted-by":"crossref","unstructured":"Wang SF, Kowal TJ, Ning K, Koo EB, Wu AY, Mahajan VB, et al. Review of ocular manifestations of Joubert syndrome. 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