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den Hollander, A.I.* ; Koenekoop, R.K.* ; Mohamed, M.D.* ; Arts, H.H.* ; Boldt, K.H.W. ; Towns, K.V.* ; Sedmak, T.* ; Beer, M. ; Nagel-Wolfrum, K.* ; McKibbin, M.* ; Dharmaraj, S.* ; Lopez, I.* ; Ivings, L.* ; Williams, G.A.* ; Springell, K.* ; Woods, C.G.* ; Jafri, H.* ; Rashid, Y.* ; Strom, T.M. ; van der Zwaag, B.* ; Gosens, I.* ; Kersten, F.F.* ; van Wijk, E.* ; Veltman, J.A.* ; Zonneveld, M.N.* ; van Beersum, S.E.* ; Maumenee, I.H.* ; Wolfrum, U.* ; Cheetham, M.E.* ; Ueffing, M. ; Cremers, F.P.* ; Inglehearn, C.F.* ; Roepman, R.*

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

Nat. Genet. 39, 889-895 (2007)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 39, Issue: 7, Pages: 889-895 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)