Abstract
Joubert syndrome–related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies.
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Acknowledgements
We thank the Marshfield Clinic Research Foundation and the US National Heart, Lung, and Blood Institute for genotyping support. We also thank C. Uggetti (Pediatric Neuroradiology, IRCCS 'C. Mondino Foundation', University of Pavia) for her contribution in reviewing MRIs of selected patients. We received help with imaging from B. Brinkman and the University of California, San Diego Neuroscience Microscopy Core and help with in situ hybridization from W. Books in the Hamilton laboratory. This work was supported by grants from the US National Institute of Neurological Disease and Stroke, the Italian Ministry of Health (Ricerca Corrente 2006; Ricerca Finalizzata 2005 Progetto Malattie Rare, Conv. 526/A36), the Fondazione Pierfranco e Luisa Mariani ONLUS, the March of Dimes, the Simons Foundation and the Burroughs Wellcome Fund Award in Translational Research.
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Supplementary information
Supplementary Fig. 1
Pedigrees of JBTS5 linked families and haplotypes spanning the linked regions. (PDF 188 kb)
Supplementary Fig. 2
Electropherograms of CEP290 mutations. (PDF 469 kb)
Supplementary Table 1
Primers and PCR conditions for CEP290 coding exons. (PDF 11 kb)
Supplementary Table 2
Clinical findings from patients with CEP290 homozygous mutations. (PDF 14 kb)
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Valente, E., Silhavy, J., Brancati, F. et al. Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet 38, 623–625 (2006). https://doi.org/10.1038/ng1805
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DOI: https://doi.org/10.1038/ng1805
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