CRB1 mutations in inherited retinal dystrophies.
Kinga M. Bujakowska,Isabelle Audo,Saddek Mohand-Said,Marie-Elise Lancelot,Marie-Elise Lancelot,Marie-Elise Lancelot,Aline Antonio,Aurore Germain,Aurore Germain,Aurore Germain,Thierry Léveillard,Thierry Léveillard,Thierry Léveillard,Mélanie Letexier,Jean-Paul Saraiva,Christine Lonjou,Wassila Carpentier,José-Alain Sahel,Shomi S. Bhattacharya,Christina Zeitz,Christina Zeitz,Christina Zeitz +21 more
TL;DR: A meta‐analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination.
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Abstract: Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients. The data from previous reports were used to analyze a potential correlation between CRB1 variants and the clinical features of respective patients. This meta-analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination.
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Photoreceptor Cilia and Retinal Ciliopathies.
TL;DR: The structure and composition of PSC and different forms of ciliopathies with retinal involvement are described and the genetics of the IRDs are reviewed, which are monogenic disorders but genetically diverse with regard to causality.
Molecular findings from 537 individuals with inherited retinal disease
Jamie M Ellingford,Jamie M Ellingford,Stephanie Barton,Sanjeev S. Bhaskar,James O'Sullivan,James O'Sullivan,Simon G. Williams,Janine A. Lamb,Binay Panda,Panagiotis I. Sergouniotis,Panagiotis I. Sergouniotis,Rachel L. Gillespie,Rachel L. Gillespie,Stephen P. Daiger,Georgina Hall,Theodora Gale,I. Christopher Lloyd,I. Christopher Lloyd,Paul N. Bishop,Paul N. Bishop,Simon C Ramsden,Graeme C.M. Black,Graeme C.M. Black +22 more
TL;DR: It is shown that clinically analysed variants indicated as rare in dbSNP and the Exome Variant Server remain rare in ExAC, and that genes discovered as a cause of IRD in the post-NGS era are rare causes ofIRD in a population of clinically surveyed individuals.
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On phagocytes and macular degeneration
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•Journal Article
Genotyping Microarray (Disease Chip) for Leber Congenital Amaurosis
Rando Allikmets,Jana Zernant,Maigi Külm,Isabelle Perrault,A.I. den Hollander,Sharola Dharmaraj,Robert K. Koenekoop,J. Kaplan,F.P.M. Cremers,Irene H. Maumenee +9 more
TL;DR: In this article, an arrayed primer extension (APEX) technology was used to design a genotyping microarray for early-onset, severe retinal degenerations that includes all of the >300 disease-associated variants currently described in eight genes (in addition to the six just listed, the earlyonset RP genes LRAT and MERTK were added).
159
Review and update on the molecular basis of Leber congenital amaurosis.
TL;DR: Historical perspective, clinical ophthalmological findings, new molecular-genetics technologies, possible phenotype-genotypes correlations, and gene therapy for some LCA genes are described.
129
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Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).
A.I. den Hollander,J.B. ten Brink,Y.J.M. de Kok,S. van Soest,L. I. van den Born,M.A. van Driel,T.J.R. van de Pol,Annette M. Payne,Shomi S. Bhattacharya,Ulrich Kellner,Carel B. Hoyng,Andries Westerveld,Han G. Brunner,E.M. Bleeker-Wagemakers,August F. Deutman,John R. Heckenlively,Frans P.M. Cremers,Arthur A.B. Bergen +17 more
TL;DR: The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration, and a role forCRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina is suggested.
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