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

Authors: den Hollander, Anneke I  Koenekoop, Robert K  Mohamed, Moin D  Arts, Heleen H  Boldt, Karsten  Towns, Katherine V  Sedmak, Tina  Beer, Monika  Nagel-Wolfrum, Kerstin  McKibbin, Martin  Dharmaraj, Sharola  Lopez, Irma  Ivings, Lenka  Williams, Grange A  Springell, Kelly  Woods, C Geoff  Jafri, Hussain  Rashid, Yasmin  Strom, Tim M  van der Zwaag, Bert  Gosens, Ilse  Kersten, Ferry F J  van Wijk, Erwin  Veltman, Joris A  Zonneveld, Marijke N  van Beersum, Sylvia E C  Maumenee, Irene H  Wolfrum, Uwe  Cheetham, Michael E  Ueffing, Marius  Cremers, Frans P M  Inglehearn, Chris F  Roepman, Ronald 
Citation: den Hollander AI, etal., Nat Genet. 2007 Jul;39(7):889-95. doi: 10.1038/ng2066. Epub 2007 Jun 3.
Pubmed: (View Article at PubMed) PMID:17546029
DOI: Full-text: DOI:10.1038/ng2066

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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CRRD Object Information
CRRD ID: 14397561
Created: 2019-04-10
Species: All species
Last Modified: 2019-04-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.