@article {926,
	title = {Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome.},
	journal = {Hum Mutat},
	volume = {41},
	year = {2020},
	month = {2020 12},
	pages = {2179-2194},
	abstract = {<p>Ciliopathies are clinically and genetically heterogeneous diseases. We studied three patients from two independent families presenting with features of Joubert syndrome: abnormal breathing pattern during infancy, developmental delay/intellectual disability, cerebellar ataxia, molar tooth sign on magnetic resonance imaging scans, and polydactyly. We identified biallelic loss-of-function (LOF) variants in CBY1, segregating with the clinical features of Joubert syndrome in the families. CBY1 localizes to the distal end of the mother centriole, contributing to the formation and function of cilia. In accordance with the clinical and mutational findings in the affected individuals, we demonstrated that depletion of Cby1 in zebrafish causes ciliopathy-related phenotypes. Levels of CBY1 transcript were found reduced in the patients compared with controls, suggesting degradation of the mutated transcript through nonsense-mediated messenger RNA decay. Accordingly, we could detect CBY1 protein in fibroblasts from controls, but not from patients by immunofluorescence. Furthermore, we observed reduced ability to ciliate, increased ciliary length, and reduced levels of the ciliary proteins AHI1 and ARL13B in patient fibroblasts. Our data show that CBY1 LOF-variants cause a ciliopathy with features of Joubert syndrome.</p>},
	issn = {1098-1004},
	doi = {10.1002/humu.24127},
	author = {Epting, Daniel and Senaratne, Lokuliyange D S and Ott, Elisabeth and Holmgren, Asbj{\o}rn and Sumathipala, Dulika and Larsen, Selma M and Wallmeier, Julia and Bracht, Diana and Frikstad, Kari-Anne M and Crowley, Suzanne and Sikiric, Alma and Bar{\o}y, Tuva and K{\"a}smann-Kellner, Barbara and Decker, Eva and Decker, Christian and Bachmann, Nadine and Patzke, Sebastian and Phelps, Ian G and Katsanis, Nicholas and Giles, Rachel and Schmidts, Miriam and Zucknick, Manuela and Lienkamp, Soeren S and Omran, Heymut and Davis, Erica E and Doherty, Dan and Str{\o}mme, Petter and Frengen, Eirik and Bergmann, Carsten and Misceo, Doriana}
}
@article {159,
	title = {Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome.},
	journal = {Elife},
	volume = {4},
	year = {2015},
	month = {2015 May 30},
	pages = {e06602},
	abstract = {<p>Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1\% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies. </p>},
	keywords = {Abnormalities, Multiple, Cell Cycle Proteins, Cerebellum, Eye Abnormalities, Gene Frequency, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Heterozygote, Humans, Kidney Diseases, Cystic, Mutant Proteins, Retina, RNA, Small Interfering},
	issn = {2050-084X},
	doi = {10.7554/eLife.06602},
	author = {Roosing, Susanne and Hofree, Matan and Kim, Sehyun and Scott, Eric and Copeland, Brett and Romani, Marta and Silhavy, Jennifer L and Rosti, Rasim O and Schroth, Jana and Mazza, Tommaso and Miccinilli, Elide and Zaki, Maha S and Swoboda, Kathryn J and Milisa-Drautz, Joanne and Dobyns, William B and Mikati, Mohamed A and {\.I}ncecik, Faruk and Azam, Matloob and Borgatti, Renato and Romaniello, Romina and Boustany, Rose-Mary and Clericuzio, Carol L and D{\textquoteright}Arrigo, Stefano and Str{\o}mme, Petter and Boltshauser, Eugen and Stanzial, Franco and Mirabelli-Badenier, Marisol and Moroni, Isabella and Bertini, Enrico and Emma, Francesco and Steinlin, Maja and Hildebrandt, Friedhelm and Johnson, Colin A and Freilinger, Michael and Vaux, Keith K and Gabriel, Stacey B and Aza-Blanc, Pedro and Heynen-Genel, Susanne and Ideker, Trey and Dynlacht, Brian D and Lee, Ji Eun and Valente, Enza Maria and Kim, Joon and Gleeson, Joseph G}
}
