| Literature DB >> 17546029 |
Anneke I den Hollander1, Robert K Koenekoop, Moin D Mohamed, Heleen H Arts, Karsten Boldt, Katherine V Towns, Tina Sedmak, Monika Beer, Kerstin Nagel-Wolfrum, Martin McKibbin, Sharola Dharmaraj, Irma Lopez, Lenka Ivings, Grange A Williams, Kelly Springell, C Geoff Woods, Hussain Jafri, Yasmin Rashid, Tim M Strom, Bert van der Zwaag, Ilse Gosens, Ferry F J Kersten, Erwin van Wijk, Joris A Veltman, Marijke N Zonneveld, Sylvia E C van Beersum, Irene H Maumenee, Uwe Wolfrum, Michael E Cheetham, Marius Ueffing, Frans P M Cremers, Chris F Inglehearn, Ronald Roepman.
Abstract
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.Entities:
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Year: 2007 PMID： 17546029 DOI： 10.1038/ng2066
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330