Leber Congenital Amaurosis and Retinitis Pigmentosa with Coats-like Exudative Vasculopathy Are Associated with Mutations in the Crumbs Homologue 1 (CRB1) Gene

Hollander, Anneke I. den; Heckenlively, John R.; Born, L. Ingeborgh van den; Kok, Y.J.M. de; Velde-Visser, S.D. van der; Kellner, Ulrich; Jurklies, Bernhard; Schooneveld, Mary J. van; Blankenagel, A.; Rohrschneider, Klaus; Wissinger, Bernd; Cruysberg, Johan R.M.; Deutman, August F.; Brunner, Han G.; Apfelstedt-Sylla, Eckart; Hoyng, Carel B.; Cremers, Frans P.M.

doi:10.1086/321263

Cited by 310 publications

(216 citation statements)

References 23 publications

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“…This observation raises the question to know whether non-truncating mutations of this gene could be involved in autosomal recessive retinal dystrophies less severe than LCA. Indeed, LCA-associated mutations are commonly deleterious mutations and mutations in several LCA genes can be responsible for autosomal recessive retinal dystrophies (retinitis pigmentosa or cone-rod dystrophies) [Gu et al, 1997;Freund et al, 1997;Banerjee et al, 1998;Sohocki et al, 1998;Lewis et al, 1999;den Hollander 1999;Lorenz et al, 2000;den Hollander et al, 2001;Sohocki et al, 2001;Thompson et al, 2001Thompson et al, , 2002Hameed et al, 2003;den Hollander et al, 2004;Janecke et al, 2004;Perrault et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

“…60%) [Perrault et al, 1999;Hanein et al, 2004]. Up to date, 13 LCA genes have been mapped, 10 of which have been identified: GUCY2D/retGC1 [Perrault et al, 1996], RPE65 [Marlhens et al, 1997], CRX [Swaroop et al, 1999], AIPL1 [Sohocki et al, 2000], RPGRIP1 [Dryja et al, 2001;Gerber et al, 2001], CRB1 [den Hollander et al, 2001;Gerber et al, 2002], LRAT [Thompson and Gal, 2003], TULP1 , RDH12 [Janecke et al, 2004;Perrault et al, 2004], CEP290 [den Hollander et al, 2006;Perrault et al, 2007]. Mutations in 3/10of them were shown to account for LCA type I (GUCY2D, RPGRIP1, CEP290) while, although less frequent, LCA type II was hitherto accounted for by mutations in 7/10 genes (RPE65, CRX, AIPL1, CRB1, LRAT TULP12, RDH12) [Perrault et al, 1999;Hanein et al, 2004;Perrault et al, 2004;Perrault et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

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Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

et al. 2007

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Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60 % of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40 % of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

et al. 2007

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“…Interactions between mammalian homologues of DmPar-6͞DaPKC and Sdt͞Crb͞Dlt complexes have just been reported (20), consistent with the colocalization of DaPKC with Sdt͞Crb͞Dlt on stalk membrane. In addition, human homologues of Crb are implicated in retinitis pigmentosa and Leber congenital amaurosis, two heritable forms of human disease of photoreceptor degeneration (21)(22)(23)(24). In Drosophila, crb photoreceptors also degenerate under intense lighting conditions (25), resembling the phenotype in human diseases.…”

Section: Discussionmentioning

confidence: 99%

Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture

Hong

Ackerman

Jan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Photoreceptors form during Drosophila pupal development and acquire elaborate membrane structures, including the rhabdomeres and stalk membranes. Here, we show that the development of these cellular structures involves two distinct processes: the establishment of apical-basal polarity that requires Bazooka (Baz), and the regionalization of apical membrane into stalk membranes and rhabdomeres that requires Stardust (Sdt). In the absence of Baz, the apical-basal polarity is compromised in early pupal photoreceptors, and no identifiable apical membrane domain is formed. Sdt, in contrast, plays a more limited role in apical-basal polarity but is essential for the proper localization of transmembrane protein Crumbs (Crb), known to be required in the biogenesis of stalk membrane. Loss of Sdt causes strong defects in stalk membrane and rhabdomere resembling crb mutant phenotype. Thus, proteins required for establishing the early embryonic epithelial polarity are used later for the morphogenesis of photoreceptors, with Baz and Sdt functioning in different aspects of the formation of the apical-basal cellular architecture. D ifferent cell types exhibit different degrees of complexity in their morphogenesis. Epithelial cells are polarized to have distinct apical versus basolateral domains. Cascades of protein complexes have been found to specify this polarity (1). Many cells that are derived from epithelial cells have more complex morphology to carry out important functions, such as photoreceptors for vision. How these cells elaborate their different membrane domains is not well understood. In Drosophila, photoreceptors have clearly recognizable apical-basal polarity demarcated by zonula adherens (ZA) (2). Is this polarity established by the same protein complexes that specify epithelial polarity? How might this apical-basal polarity specification influence other structural specializations, e.g., the elaboration of rhabdomere perpendicular to the apical-basal axis? And, what are the mechanisms for regionalizing specific membrane domains in conjunction with the polarity?One approach to address these questions in Drosophila is to test whether similar organizations of genetic pathways in simple and relatively well studied embryonic epithelial polarity also underlie the development of polarity in more specialized cell types like photoreceptors. Drosophila embryonic epithelium represents one of the simplest polarized cell types, and its apical-basal polarity is controlled largely in concert by three protein complexes (1). Baz(DmPar-3)͞DmPar-6͞DaPKC (atypical protein kinase C) plays the earliest and essential role in initiating the apical-basal polarity, whereas Sdt͞Crb͞Dlt (Discs lost) maintains the ZA formation and polarity by counteracting the activity of Dlg (Discs large)͞Lgl (Lethal giant larvae)͞Scrib (Scribble) (3, 4). Except for DaPKC, Crumbs (Crb), and Lgl, all of these proteins contain one or more PDZ domains important for mediating protein-protein interactions (1). The first insight that at least some of these protei...

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“…All previous reported cases have been associated with mutations in CRB1. 10 Further studies are required to confirm the efficacy of the dexamethasone intravitreal implant in this rare condition.…”

Section: Discussionmentioning

confidence: 98%

Coat’s-like exudation in rhodopsin retinitis pigmentosa: successful treatment with an intravitreal dexamethasone implant

Patil

Lotery

2014

Eye

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Purpose Role of intravitreal injection of dexamethasone implant (Ozurdex) for refractory macular thickening. Methods A case report of a 13-year-old boy with Rhodopsin-positive, CRB1-negative retinitis pigmentosa presenting with Coat's-like exudative vitreoretinopathy and treatment-resistant cystoid macular oedema. Results A reduction in the macular thickening following a single injection of Ozurdex. Conclusion We present our experience in successful treatment of refractory macular oedema with intravitreal injection of dexamethasone implant resulting in clinically significant resolution of macular thickening.

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Leber Congenital Amaurosis and Retinitis Pigmentosa with Coats-like Exudative Vasculopathy Are Associated with Mutations in the Crumbs Homologue 1 (CRB1) Gene

Cited by 310 publications

References 23 publications

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture

Coat’s-like exudation in rhodopsin retinitis pigmentosa: successful treatment with an intravitreal dexamethasone implant

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