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Gene Review

CRB1  -  crumbs family member 1, photoreceptor...

Homo sapiens

Synonyms: LCA8, Protein crumbs homolog 1, RP12
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Disease relevance of CRB1


High impact information on CRB1

  • The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration [6].
  • Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis [7].
  • Our findings suggest that CRB1 mutations are a frequent cause of LCA and are strongly associated with the development of Coats-like exudative vasculopathy in patients with RP [8].
  • We demonstrate that the Crb1-/- phenotype, as shown in Crb1-/- mice, is accelerated and intensified in primary retina cultures [1].
  • Human CRB1 and its two paralogues, CRB2 and CRB3, are highly conserved throughout the animal kingdom [9].

Biological context of CRB1

  • In exon 9 of the CRB1 gene a T to C transversion was found in the family suffering from LCA (010LCA).The LCA phenotype of another family (011LCA) in which the CRB1 locus was excluded, showed linkage with microsatellite markers D17S1294 and D17S796 on chromosome 17p13 [10].
  • In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1 [6].
  • In total, 71 different sequence variants have been identified on 184 CRB1 alleles of patients with retinal dystrophies, including amino acid substitutions, frameshift, nonsense, and splice site mutations, in-frame deletions, and large insertions [11].
  • As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene [12].
  • Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped [12].

Anatomical context of CRB1


Other interactions of CRB1

  • The molecular data for CRB1 and RPE65 support previous hypotheses that LCA can represent the severe end of a spectrum of retinal dystrophies [13].
  • Mutations were most frequently found in CRB1 (15.5%), followed by GUCY2D (10.3%) [14].
  • CONCLUSIONS: These data imply that MPP4 and -5 have a role in photoreceptor polarity and, by association with CRB1, pinpoint the cognate genes as functional candidate genes for inherited retinopathies [15].
  • MPP5 recruits MPP4 to the CRB1 complex in photoreceptors [15].
  • The present study establishes a genotype-phenotype correlation for AIPL1, CRB1, and GUCY2D [14].

Analytical, diagnostic and therapeutic context of CRB1

  • Recent studies in two animal models, mouse and Drosophila, and in vivo high-resolution microscopy in patients with LCA, have shed light on the role of CRB1 in the pathogenesis of retinal dystrophies and its function in the photoreceptors [11].
  • METHODS: Seven unrelated heterozygous carriers of CRB1 mutations underwent phenotyping by full eye examinations (indirect ophthalmoscopy and slit lamp biomicroscopy) and functional testing (standard full-field electroretinography [ERG] and multifocal ERG) [16].
  • All 12 coding exons and the 5' promoter region of the crumbs homologue 1 (CRB1) gene were PCR amplified and DNA sequenced [17].


  1. Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Muller glia cells. van Rossum, A.G., Aartsen, W.M., Meuleman, J., Klooster, J., Malysheva, A., Versteeg, I., Arsanto, J.P., Le Bivic, A., Wijnholds, J. Hum. Mol. Genet. (2006) [Pubmed]
  2. Crumbs homologue 1 is required for maintenance of photoreceptor cell polarization and adhesion during light exposure. van de Pavert, S.A., Kantardzhieva, A., Malysheva, A., Meuleman, J., Versteeg, I., Levelt, C., Klooster, J., Geiger, S., Seeliger, M.W., Rashbass, P., Le Bivic, A., Wijnholds, J. J. Cell. Sci. (2004) [Pubmed]
  3. A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis. Abouzeid, H., Li, Y., Maumenee, I.H., Dharmaraj, S., Sundin, O. Ophthalmic Genet. (2006) [Pubmed]
  4. Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Jacobson, S.G., Cideciyan, A.V., Aleman, T.S., Pianta, M.J., Sumaroka, A., Schwartz, S.B., Smilko, E.E., Milam, A.H., Sheffield, V.C., Stone, E.M. Hum. Mol. Genet. (2003) [Pubmed]
  5. Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration. Johnson, K., Grawe, F., Grzeschik, N., Knust, E. Curr. Biol. (2002) [Pubmed]
  6. Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). den Hollander, A.I., ten Brink, J.B., de Kok, Y.J., van Soest, S., van den Born, L.I., van Driel, M.A., van de Pol, D.J., Payne, A.M., Bhattacharya, S.S., Kellner, U., Hoyng, C.B., Westerveld, A., Brunner, H.G., Bleeker-Wagemakers, E.M., Deutman, A.F., Heckenlively, J.R., Cremers, F.P., Bergen, A.A. Nat. Genet. (1999) [Pubmed]
  7. Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C.J., Ready, D.F., Tepass, U. Nature (2002) [Pubmed]
  8. Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. den Hollander, A.I., Heckenlively, J.R., van den Born, L.I., de Kok, Y.J., van der Velde-Visser, S.D., Kellner, U., Jurklies, B., van Schooneveld, M.J., Blankenagel, A., Rohrschneider, K., Wissinger, B., Cruysberg, J.R., Deutman, A.F., Brunner, H.G., Apfelstedt-Sylla, E., Hoyng, C.B., Cremers, F.P. Am. J. Hum. Genet. (2001) [Pubmed]
  9. Towards understanding CRUMBS function in retinal dystrophies. Richard, M., Roepman, R., Aartsen, W.M., van Rossum, A.G., den Hollander, A.I., Knust, E., Wijnholds, J., Cremers, F.P. Hum. Mol. Genet. (2006) [Pubmed]
  10. Mutation screening of Pakistani families with congenital eye disorders. Khaliq, S., Abid, A., Hameed, A., Anwar, K., Mohyuddin, A., Azmat, Z., Shami, S.A., Ismail, M., Mehdi, S.Q. Exp. Eye Res. (2003) [Pubmed]
  11. CRB1 mutation spectrum in inherited retinal dystrophies. den Hollander, A.I., Davis, J., van der Velde-Visser, S.D., Zonneveld, M.N., Pierrottet, C.O., Koenekoop, R.K., Kellner, U., van den Born, L.I., Heckenlively, J.R., Hoyng, C.B., Handford, P.A., Roepman, R., Cremers, F.P. Hum. Mutat. (2004) [Pubmed]
  12. A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis. Gerber, S., Perrault, I., Hanein, S., Shalev, S., Zlotogora, J., Barbet, F., Ducroq, D., Dufier, J., Munnich, A., Rozet, J., Kaplan, J. Ophthalmic Genet. (2002) [Pubmed]
  13. Molecular genetics of Leber congenital amaurosis. Cremers, F.P., van den Hurk, J.A., den Hollander, A.I. Hum. Mol. Genet. (2002) [Pubmed]
  14. Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis. Yzer, S., Leroy, B.P., De Baere, E., de Ravel, T.J., Zonneveld, M.N., Voesenek, K., Kellner, U., Ciriano, J.P., de Faber, J.T., Rohrschneider, K., Roepman, R., den Hollander, A.I., Cruysberg, J.R., Meire, F., Casteels, I., van Moll-Ramirez, N.G., Allikmets, R., van den Born, L.I., Cremers, F.P. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  15. MPP5 recruits MPP4 to the CRB1 complex in photoreceptors. Kantardzhieva, A., Gosens, I., Alexeeva, S., Punte, I.M., Versteeg, I., Krieger, E., Neefjes-Mol, C.A., den Hollander, A.I., Letteboer, S.J., Klooster, J., Cremers, F.P., Roepman, R., Wijnholds, J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  16. CRB1 heterozygotes with regional retinal dysfunction: implications for genetic testing of leber congenital amaurosis. Yzer, S., Fishman, G.A., Racine, J., Al-Zuhaibi, S., Chakor, H., Dorfman, A., Szlyk, J., Lachapelle, P., van den Born, L.I., Allikmets, R., Lopez, I., Cremers, F.P., Koenekoop, R.K. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  17. Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene. McKay, G.J., Clarke, S., Davis, J.A., Simpson, D.A., Silvestri, G. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
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