6533b7d5fe1ef96bd1263e38
RESEARCH PRODUCT
Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis
Lenka IvingsMartin MckibbinUwe WolfrumErwin Van WijkFerry F.j. KerstenBert Van Der ZwaagMichael E. CheethamTim M. StromG. A. WilliamsSylvia E. C. Van BeersumChris F. InglehearnSharola DharmarajMarius UeffingTina SedmakFrans P.m. CremersC. Geoff WoodsJoris A. VeltmanMarijke N. ZonneveldMoin MohamedMoin MohamedKarsten BoldtRonald RoepmanHeleen H. ArtsIrene H. MaumeneeKerstin Nagel-wolfrumIrma LopezHussain JafriYasmin RashidMonika BeerIlse GosensAnneke I. Den HollanderKatherine V. TownsKelly SpringellRobert K. Koenekoopsubject
MaleCandidate geneGenetics and epigenetic pathways of disease [NCMLS 6]genetic structuresMolecular Sequence DataOptic Atrophy Hereditary LeberNeuroinformatics [DCN 3]Biologymedicine.disease_causeCiliopathiesJoubert syndromeCell LineFrameshift mutationGenomic disorders and inherited multi-system disorders [IGMD 3]MiceTranslational research [ONCOL 3]Chlorocebus aethiopsPerception and Action [DCN 1]GeneticsmedicineNeurosensory disorders [UMCN 3.3]AnimalsHumansCiliaRats WistarEye ProteinsFrameshift MutationRenal disorder [IGMD 9]GeneticsMutationCiliumDisease gene identificationmedicine.diseasePhenotypeeye diseasesPedigreeRatsMice Inbred C57BLGenetic defects of metabolism [UMCN 5.1]Codon NonsenseCOS CellsFemalesense organsFunctional Neurogenomics [DCN 2]Microtubule-Associated Proteinsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-01-01 | Nature Genetics |