Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis
| Autor: | Lenka Ivings, Martin McKibbin, Uwe Wolfrum, Erwin van Wijk, Ferry F.J. Kersten, Bert van der Zwaag, Michael E. Cheetham, Tim M. Strom, G. A. Williams, Sylvia E. C. van Beersum, Chris F. Inglehearn, Sharola Dharmaraj, Marius Ueffing, Tina Sedmak, Frans P.M. Cremers, C. Geoff Woods, Joris A. Veltman, Marijke N. Zonneveld, Moin Mohamed, Karsten Boldt, Ronald Roepman, Heleen H. Arts, Irene H. Maumenee, Kerstin Nagel-Wolfrum, Irma Lopez, Hussain Jafri, Yasmin Rashid, Monika Beer, Ilse Gosens, Anneke I. den Hollander, Katherine V. Towns, Kelly Springell, Robert K. Koenekoop |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Candidate gene Genetics and epigenetic pathways of disease [NCMLS 6] genetic structures Molecular Sequence Data Optic Atrophy Hereditary Leber Neuroinformatics [DCN 3] Biology medicine.disease_cause Ciliopathies Joubert syndrome Cell Line Frameshift mutation Genomic disorders and inherited multi-system disorders [IGMD 3] Mice Translational research [ONCOL 3] Chlorocebus aethiops Perception and Action [DCN 1] Genetics medicine Neurosensory disorders [UMCN 3.3] Animals Humans Cilia Rats Wistar Eye Proteins Frameshift Mutation Renal disorder [IGMD 9] Mutation Cilium Disease gene identification medicine.disease Phenotype eye diseases Pedigree Rats Mice Inbred C57BL Genetic defects of metabolism [UMCN 5.1] Codon Nonsense COS Cells Female sense organs Functional Neurogenomics [DCN 2] Microtubule-Associated Proteins |
| Zdroj: | Nature Genetics, 39, 7, pp. 889-95 Nature Genetics, 39, 889-95 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng2066 |
| Popis: | Contains fulltext : 53618.pdf (Publisher’s version ) (Closed access) Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA. |
| Databáze: | OpenAIRE |
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