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Your search keyword '"Elide Miccinilli"' showing total 4 results
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4 results on '"Elide Miccinilli"'

1. Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome

Author

Susanne Roosing, Matan Hofree, Sehyun Kim, Eric Scott, Brett Copeland, Marta Romani, Jennifer L Silhavy, Rasim O Rosti, Jana Schroth, Tommaso Mazza, Elide Miccinilli, Maha S Zaki, Kathryn J Swoboda, Joanne Milisa-Drautz, William B Dobyns, Mohamed A Mikati, Faruk İncecik, Matloob Azam, Renato Borgatti, Romina Romaniello, Rose-Mary Boustany, Carol L Clericuzio, Stefano D'Arrigo, Petter Strømme, Eugen Boltshauser, Franco Stanzial, Marisol Mirabelli-Badenier, Isabella Moroni, Enrico Bertini, Francesco Emma, Maja Steinlin, Friedhelm Hildebrandt, Colin A Johnson, Michael Freilinger, Keith K Vaux, Stacey B Gabriel, Pedro Aza-Blanc, Susanne Heynen-Genel, Trey Ideker, Brian D Dynlacht, Ji Eun Lee, Enza Maria Valente, Joon Kim, and Joseph G Gleeson

Subjects
Joubert syndrome, ciliopathy, siRNA, high-content screen, KIAA0586, Talpid3, Medicine, Science, Biology (General), QH301-705.5
Abstract

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.

Published
2015
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2. Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

Author

Alessia Micalizzi, Maja Steinlin, Patrizia Accorsi, Lorenzo Pinelli, Serdar Ceylaner, Eugen Boltshauser, Renato Borgatti, Franco Stanzial, Ronen Spiegel, Emanuela Avola, P Póo, Enrico Bertini, Tommaso Mazza, Giangennaro Coppola, Mario Lituania, Andrea Poretti, Loreto Martorell, Marta Romani, Nicole I. Wolf, Andreas R. Janecke, Sabrina Signorini, Elide Miccinilli, Kathrin Ludwig, Brahim Tabarki, Romina Romaniello, Sylvie Odent, Alessandro Simonati, Margherita Santucci, Francesca Mancini, Stefano D'Arrigo, Federica Zibordi, Enza Maria Valente, Lucio Giordano, Romani, Marta, Mancini, Francesca, Micalizzi, Alessia, Poretti, Andrea, Miccinilli, Elide, Accorsi, Patrizia, Avola, Emanuela, Bertini, Enrico, Borgatti, Renato, Romaniello, Romina, Ceylaner, Serdar, Coppola, Giangennaro, D’Arrigo, Stefano, Giordano, Lucio, Janecke, Andreas R., Lituania, Mario, Ludwig, Kathrin, Martorell, Loreto, Mazza, Tommaso, Odent, Sylvie, Pinelli, Lorenzo, Poo, Pilar, Santucci, Margherita, Signorini, Sabrina, Simonati, Alessandro, Spiegel, Ronen, Stanzial, Franco, Steinlin, Maja, Tabarki, Brahim, Wolf, Nicole I., Zibordi, Federica, Boltshauser, Eugen, Valente, Enza Maria, Cytogenetics, INGEMM, Institute of Medical and Molecular Genetics, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Division of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence Medical School, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Neurological and Visual Sciences, University of Verona (UNIVR), Servizio aziendale di Consulenza Genetica, Ospedale di Bolzano, Pediatric surgery, NCA - Brain mechanisms in health and disease, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli Studi di Firenze = University of Florence (UniFI), and Università degli studi di Verona = University of Verona (UNIVR)

Subjects
Male, Proband, Oral-facial-digital type VI syndrome, [SDV]Life Sciences [q-bio], Joubert syndrome, C5orf42 gene, medicine.disease_cause, Cohort Studies, Cerebellum, Genetics(clinical), Eye Abnormalities, 610 Medicine & health, Orofaciodigital Syndrome, Membrane Protein, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Genetics, 0303 health sciences, Mutation, Polydactyly, 030305 genetics & heredity, Hypothalamic Disease, Cerebellar Disease, Kidney Diseases, Cystic, Orofaciodigital Syndromes, Major gene, Phenotype, Kidney Diseases, Female, Hypothalamic Diseases, Human, Hamartoma, Short Report, Biology, Retina, Follow-Up Studie, Cystic, 03 medical and health sciences, Genetic, Hypothalamic hamartoma, Cerebellar Diseases, Family, Follow-Up Studies, Humans, Membrane Proteins, medicine, Abnormalities, Multiple, 030304 developmental biology, medicine.disease, Eye Abnormalitie, Cohort Studie
Abstract

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients. Electronic supplementary material The online version of this article (doi:10.1007/s00439-014-1508-3) contains supplementary material, which is available to authorized users.

Published
2014
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3. Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome

Author

Faruk Incecik, Brian David Dynlacht, Enza Maria Valente, Ji Eun Lee, Susanne Roosing, Eric Scott, Brett Copeland, Colin A. Johnson, Trey Ideker, Renato Borgatti, Isabella Moroni, William B. Dobyns, Petter Strømme, Pedro Aza-Blanc, Joseph G. Gleeson, Rasim Ozgur Rosti, Susanne Heynen-Genel, Maja Steinlin, Eugen Boltshauser, Joon Kim, Elide Miccinilli, Joanne Milisa-Drautz, Stefano D'Arrigo, Keith K. Vaux, Carol L. Clericuzio, M. Mirabelli-Badenier, Romina Romaniello, Enrico Bertini, Tommaso Mazza, Michael Freilinger, Sehyun Kim, Matan Hofree, Maha S. Zaki, Jennifer L. Silhavy, Kathryn J. Swoboda, Mohamed A Mikati, Rose-Mary Boustany, Marta Romani, Friedhelm Hildebrandt, Stacey Gabriel, Franco Stanzial, Matloob Azam, Jana Schroth, Francesco Emma, Çukurova Üniversitesi, University of Zurich, and Gleeson, Joseph G

Subjects
Cell Cycle Proteins, medicine.disease_cause, Ciliopathies, 0302 clinical medicine, Gene Frequency, 2400 General Immunology and Microbiology, Cerebellum, Eye Abnormalities, Biology (General), RNA, Small Interfering, Exome, Genetics, 0303 health sciences, Mutation, education.field_of_study, General Neuroscience, Cilium, 2800 General Neuroscience, General Medicine, Kidney Diseases, Cystic, high-content screen, 3. Good health, KIAA0586, Medicine, Research Article, Heterozygote, QH301-705.5, Science, Population, 610 Medicine & health, Biology, General Biochemistry, Genetics and Molecular Biology, Joubert syndrome, Retina, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Talpid3, Ciliogenesis, medicine, Humans, Abnormalities, Multiple, Genetic Predisposition to Disease, human, Genetic Testing, education, Sensory disorders Radboud Institute for Molecular Life Sciences [Radboudumc 12], Human Biology and Medicine, 030304 developmental biology, General Immunology and Microbiology, medicine.disease, Ciliopathy, Developmental Biology and Stem Cells, ciliopathy, 10036 Medical Clinic, siRNA, Mutant Proteins, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

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. DOI: http://dx.doi.org/10.7554/eLife.06602.001, eLife digest Joubert syndrome is a rare disorder that affects the brain and causes physical, mental, and sometimes visual impairments. In individuals with this condition, two parts of the brain called the cerebellar vermis and the brainstem do not develop properly. This is thought to be due to defects in the development and maintenance of tiny hair-like structures called cilia, which are found on the surface of cells. Currently, mutations in 25 different genes are known to be able to cause Joubert syndrome. However, these mutations only account for around 50% of the cases that have been studied, and the ‘unexplained’ cases suggest that mutations in other genes may also cause the disease. Here, Roosing et al. used a technique called a ‘genome-wide siRNA screen’ to identify other genes regulating the formation of cilia that might also be connected with Joubert syndrome. This approach identified almost 600 candidate genes. The data from the screen were combined with gene sequence data from 145 individuals with unexplained Joubert syndrome. Roosing et al. found that individuals with Joubert syndrome from 15 different families had mutations in a gene called KIAA0586. In chickens and mice, this gene—known as Talpid3—is required for the formation of cilia. Roosing et al.'s findings reveal a new gene that is involved in Joubert syndrome and also provides a list of candidate genes for future studies of other conditions caused by defects in the formation of cilia. The next challenges are to find out what causes the remaining unexplained cases of the disease and to understand what roles the genes identified in this study play in cilia. DOI: http://dx.doi.org/10.7554/eLife.06602.002

Published
2015

4. Author response: Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome

Author

Trey Ideker, Isabella Moroni, Colin A. Johnson, Pedro Aza-Blanc, Renato Borgatti, Stefano D'Arrigo, Keith K. Vaux, Enza Maria Valente, Susanne Heynen-Genel, Elide Miccinilli, Sehyun Kim, Petter Strømme, Joanne Milisa-Drautz, Matan Hofree, Franco Stanzial, Rose-Mary Boustany, Jennifer L. Silhavy, Carol L. Clericuzio, Eugen Boltshauser, Maja Steinlin, Enrico Bertini, Tommaso Mazza, Brian David Dynlacht, Stacey Gabriel, Susanne Roosing, Brett Copeland, Mohamed A Mikati, Romina Romaniello, Rasim Ozgur Rosti, Eric Scott, Jana Schroth, Kathryn J. Swoboda, Michael Freilinger, William B. Dobyns, Matloob Azam, Friedhelm Hildebrandt, Francesco Emma, Joon Kim, Jieun Lee, Marta Romani, M. Mirabelli-Badenier, Maha S. Zaki, Joseph G. Gleeson, and Faruk Incecik

Subjects
Genetics, medicine, Biology, medicine.disease, Genome, Joubert syndrome
Published
2015
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