Sökning: onr:"swepub:oai:DiVA.org:umu-82273" > Screening of a Larg...
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000 | 05524naa a2200781 4500 | |
001 | oai:DiVA.org:umu-82273 | |
003 | SwePub | |
008 | 131029s2013 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-822732 URI |
024 | 7 | a https://doi.org/10.1002/humu.223982 DOI |
040 | a (SwePub)umu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Mackay, Donna S4 aut |
245 | 1 0 | a Screening of a Large Cohort of Leber Congenital Amaurosis and Retinitis Pigmentosa Patients Identifies Novel LCA5 Mutations and New Genotype-Phenotype Correlations |
264 | c 2013-09-17 | |
264 | 1 | b John Wiley & Sons,c 2013 |
338 | a print2 rdacarrier | |
520 | a This study was undertaken to investigate the prevalence of sequence variants in LCA5 in patients with Leber congenital amaurosis (LCA), early-onset retinal dystrophy (EORD), and autosomal recessive retinitis pigmentosa (arRP); to delineate the ocular phenotypes; and to provide an overview of all published LCA5 variants in an online database. Patients underwent standard ophthalmic evaluations after providing informed consent. In selected patients, optical coherence tomography (OCT) and fundus autofluorescence imaging were possible. DNA samples from 797 unrelated patients with LCA and 211 with the various types of retinitis pigmentosa (RP) were screened by Sanger sequence analysis of all LCA5 exons and intron/exon junctions. Some LCA patients were prescreened by APEX technology or selected based on homozygosity mapping. In silico analyses were performed to assess the pathogenicity of the variants. Segregation analysis was performed where possible. Published and novel LCA5 variants were collected, amended for their correct nomenclature, and listed in a Leiden Open Variation Database (LOVD). Sequence analysis identified 18 new probands with 19 different LCA5 variants. Seventeen of the 19 LCA5 variants were novel. Except for two missense variants and one splice site variant, all variants were protein-truncating mutations. Most patients expressed a severe phenotype, typical of LCA. However, some LCA subjects had better vision and intact inner segment/outer segment (IS/OS) junctions on OCT imaging. In two families with LCA5 variants, the phenotype was more compatible with EORD with affected individuals displaying preserved islands of retinal pigment epithelium. One of the families with a milder phenotype harbored a homozygous splice site mutation; a second family was found to have a combination of a stop mutation and a missense mutation. This is the largest LCA5 study to date. We sequenced 1,008 patients (797 with LCA, 211 with arRP) and identified 18 probands with LCA5 mutations. Mutations in LCA5 are a rare cause of childhood retinal dystrophy accounting for ∼2% of disease in this cohort, and the majority of LCA5 mutations are likely null. The LCA5 protein truncating mutations are predominantly associated with LCA. However, in two families with the milder EORD, the LCA5 gene analysis revealed a homozygous splice site mutation in one and a stop mutation in combination with a missense mutation in a second family, suggesting that this milder phenotype is due to residual function of lebercilin and expanding the currently known phenotypic spectrum to include the milder early onset RP. Some patients have remaining foveal cone structures (intact IS/OS junctions on OCT imaging) and remaining visual acuities, which may bode well for upcoming treatment trials. | |
653 | a LCA | |
653 | a RP | |
653 | a retinal dystrophy | |
653 | a blindness | |
653 | a LCA5 | |
653 | a lebercilin | |
700 | 1 | a Borman, Arundhati Dev4 aut |
700 | 1 | a Sui, Ruifang4 aut |
700 | 1 | a van den Born, L Ingeborgh4 aut |
700 | 1 | a Berson, Eliot L4 aut |
700 | 1 | a Ocaka, Louise A4 aut |
700 | 1 | a Davidson, Alice E4 aut |
700 | 1 | a Heckenlively, John R4 aut |
700 | 1 | a Branham, Kari4 aut |
700 | 1 | a Ren, Huanan4 aut |
700 | 1 | a Lopez, Irma4 aut |
700 | 1 | a Maria, Maleeha4 aut |
700 | 1 | a Azam, Maleeha4 aut |
700 | 1 | a Henkes, Arjen4 aut |
700 | 1 | a Blokland, Ellen4 aut |
700 | 1 | a Andreasson, Sten4 aut |
700 | 1 | a de Baere, Elfride4 aut |
700 | 1 | a Bennett, Jean4 aut |
700 | 1 | a Chader, Gerald J4 aut |
700 | 1 | a Berger, Wolfgang4 aut |
700 | 1 | a Golovleva, Irinau Umeå universitet,Medicinsk och klinisk genetik4 aut0 (Swepub:umu)irgo0001 |
700 | 1 | a Greenberg, Jacquie4 aut |
700 | 1 | a den Hollander, Anneke I4 aut |
700 | 1 | a Klaver, Caroline C W4 aut |
700 | 1 | a Klevering, B Jeroen4 aut |
700 | 1 | a Lorenz, Birgit4 aut |
700 | 1 | a Preising, Markus N4 aut |
700 | 1 | a Ramsear, Raj4 aut |
700 | 1 | a Roberts, Lisa4 aut |
700 | 1 | a Roepman, Ronald4 aut |
700 | 1 | a Rohrschneider, Klaus4 aut |
700 | 1 | a Wissinger, Bernd4 aut |
700 | 1 | a Qamar, Raheel4 aut |
700 | 1 | a Webster, Andrew R4 aut |
700 | 1 | a Cremers, Frans P M4 aut |
700 | 1 | a Moore, Anthony T4 aut |
700 | 1 | a Koenekoop, Robert K4 aut |
710 | 2 | a Umeå universitetb Medicinsk och klinisk genetik4 org |
773 | 0 | t Human Mutationd : John Wiley & Sonsg 34:11, s. 1537-1546q 34:11<1537-1546x 1059-7794x 1098-1004 |
856 | 4 | u https://europepmc.org/articles/pmc4337959?pdf=render |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-82273 |
856 | 4 8 | u https://doi.org/10.1002/humu.22398 |
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