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CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders |
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| Authors: | Brancati Francesco,Barrano Giuseppe,Silhavy Jennifer L,Marsh Sarah E,Travaglini Lorena,Bielas Stephanie L,Amorini Maria,Zablocka Dominika,Kayserili Hulya,Al-Gazali Lihadh,Bertini Enrico,Boltshauser Eugen,D'Hooghe Marc,Fazzi Elisa,Fenerci Elif Y,Hennekam Raoul C M,Kiss Andrea,Lees Melissa M,Marco Elysa,Phadke Shubha R,Rigoli Luciana,Romano Stephane,Salpietro Carmelo D,Sherr Elliott H,Signorini Sabrina,Stromme Petter,Stuart Bernard,Sztriha Laszlo,Viskochil David H,Yuksel Adnan,Dallapiccola Bruno International JSRD Study Group,Valente Enza Maria,Gleeson Joseph G |
| Affiliation: | a From the IRCCS CSS, Mendel Institute, Rome, Italy b Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy c Department of Laboratory Medicine, Molecular Medicine Unit, IRCCS Bambino Gesù Hospital, Rome, Italy c CeSI, Aging Research Centre, and Department of Biomedical Sciences, G. d’Annunzio University Foundation, Chieti, Italy d Department of Neurosciences, Neurogenetics Laboratory, University of California-San Diego, La Jolla, CA e Department of Medical and Surgical Paediatric Sciences, Operative Unit of Paediatric Genetics and Immunology, University of Messina, Messina, Italy f Medical Genetics Department, Istanbul Medical Faculty, Istanbul University, Istanbul g Department of Genetics, Istanbul University Cerrahpasa Medical School, Istanbul h Department of Medical Biology, Istanbul University Cerrahpasa Medical School, Istanbul i Department of Pediatrics, Faculty of Medicine and Health Sciences, Al Ain, United Arab Emirates j Department of Neurology, Children’s University Hospital, Zurich, Switzerland j Department of Neurology, Sint-Jan Hospital, Brugge, Belgium k Department of Child Neurology and Psychiatry, IRCCS “C. Mondino Foundation,” University of Pavia, Pavia, Italy l Clinical and Molecular Genetics, Institute of Child Health, London m Department of Morphological Sciences, Federal Faculty Foundation of Medical Sciences, Porto Alegre, Brazil n Department of Neurology, University of California-San Francisco, San Francisco o Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India p Département de Pédiatrie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France q Department of Paediatrics, Faculty Division, Ullevål University Hospital, Oslo, Norway r University College Dublin Department of Obstetrics &; Gynaecology, Coombe Women’s Hospital, Dublin s Department of Paediatrics, Division B, University of Szeged, Szeged, Hungary t and Department of Pediatric Administration, University of Utah School of Medicine, Salt Lake City |
| Abstract: | Joubert syndrome–related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies. |
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