Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase
Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase(573 views) Esposito G, De Falco F, Tinto N, Testa F, Vitagliano L, Tandurella IC, Iannone L, Rossi S, Rinaldi E, Simonelli F, Zagari A, Salvatore F
Hum Mutat (ISSN: 1059-7794, 1098-1004, 1098-1004electronic), 2011 Dec; 32(12): 1460-1469.
Keywords: Chm, Choroideremia, Modeling, Rab Proteins, Amino Acid, Messenger Rna, Rab Escort Protein 1, Unclassified Drug, Alternative Rna Splicing, Article, Clinical Article, Controlled Study, Female, Human, Human Cell, Human Tissue, In Vitro Study, Italy, Missense Mutation, Mutational Analysis, Photoreceptor, Priority Journal, Protein Function, Protein Structure, Adaptor Proteins, Signal Transducing, Adult, Alkyl And Aryl Transferases, Child, Preschool, Dna Mutational Analysis, Middle Aged, Young Adult, Genetics, Metabolism, Physiopathology, Methods,
Affiliations: *** IBB - CNR ***
CEINGE-Biotecnologie Avanzate S.C.a r.l., Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy
IRCCS-Fondazione SDN, Via E. Gianturco, Naples, Italy
Dipartimento di Oftalmologia, Seconda Università di Napoli, Naples, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
Dipartimento delle Scienze Biologiche-Sezione Biostrutture, CNISM, Università di Napoli Federico II, Naples, Italy
References: Ali, B.R., Seabra, M.C., Targeting of Rab GTPases to cellular membranes (2005) Biochem Soc Trans, 33, pp. 652-65
Baron, R.A., Seabra, M., Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate (2008) Biochem J, 415, pp. 67-75
Beaufrère, L., Tuffery, S., Hamel, C., Bareil, C., Arnaud, B., Demaille, J., Claustres, M., The protein truncation test (PTT) as a method of detection for choroideremia mutations (1997) Exp Eye Res, 65, pp. 849-854
Beaufrère, L., Claustres, M., Tuffery, S., No missense mutation in choroideremia patients analyzed to date (1999) Ophthalmic Genet, 20, pp. 89-93
Cremers, F.P., Armstrong, S.A., Seabra, M.C., Brown, M.S., Goldstein, J.L., REP-2, a Rab escort protein encoded by the choroideremia-like gene (1994) J Biol Chem, 269, pp. 2111-2117
Cremers, F.P., van de Pol, D.J., van Kerkhoff, L.P., Wieringa, B., Ropers, H.H., Cloning of a gene that is rearranged in patients with choroideraemia (1990) Nature, 347, pp. 674-677
Ferreiro, V., Szijan, I., Giliberto, F., Detection of germline mosaicism in two Duchenne muscular dystrophy families using polymorphic dinucleotide (CA) n repeat loci within the dystrophin gene (2004) Mol Diagn, 8, pp. 115-121
Garcia-Hoyos, M., Lorda-Sanchez, I., Gomez-Garre, P., Villaverde, C., Cantalapiedra, D., Bustamante, A., Ego-Alvarez, D., Ayuso, C., New type of mutations in three Spanish families with choroideremia (2008) Invest Ophthalmol Vis Sci, 49, pp. 1315-1321
García-Hoyos, M., Sanz, R., Diego-Alvarez, D., Lorda-Sánchez, I., Trujillo-Tiebas, M.J., Cantalapiedra, D., Ramos, C., Ayuso, C., New approach for the refinement of the location of the X-chromosome breakpoint in a previously described female patient with choroideremia carrying a X
4 translocation (2005) Am J Med Genet A, 138, pp. 365-368
Goldberg, A.L., Protein degradation and protection against misfolded or damaged proteins (2003) Nature, 426, pp. 895-899
Guo, Z., Wu, Y.W., Das, D., Delon, C., Cramer, J., Yu, S., Thuns, S., Blankenfeldt, W., Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation (2008) EMBO J, 27, pp. 2444-2456
Jayasundera, T., Branham, K.E., Othman, M., Rhoades, W.R., Karoukis, A.J., Khanna, H., Swaroop, A., Heckenlively, J.R., RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa (2010) Arch Ophthalmol, 128, pp. 915-923
Larijani, B., Hume, A.N., Tarafder, A.K., Seabra, M.C., Multiple factors contribute to inefficient prenylation of Rab27a in Rab prenylation diseases (2003) J Biol Chem, 278, pp. 46798-46804
Lee, T.K., McTaggart, K.E., Sieving, P.A., Heckenlively, J.R., Levin, A.V., Greenberg, J., Weleber, R.G., MacDonald, I.M., Clinical diagnoses that overlap with choroideremia (2003) Can J Ophthalmol, 38, pp. 364-372
Leung, K.F., Baron, R., Seabra, M.C., Thematic review series: lipid posttranslational modifications. Geranylgeranylation of Rab GTPases (2006) J Lipid Res, 47, pp. 467-475
MacDonald, I.M., Mah, D.Y., Ho, Y.K., Lewis, R.A., Seabra, M.C., A practical diagnostic test for choroideremia (1998) Ophthalmology, 105, pp. 1637-1640
MacDonald, I.M., Seabra, M.C., Choroideremia (2006) Principles and practice of clinical electrophysiology of vision, pp. 777-779. , In: Heckenlively JR, Arden GB, editors. 2nd ed. Cambridge: Massachusetts Institute of Technology Press
Mort, M., Ivanov, D., Cooper, D.N., Chuzhanova, N.A., A meta-analysis of nonsense mutations causing human genetic disease (2008) Hum Mutat, 29, pp. 1037-1047
Newton, C.R., Graham, A., Heptinstall, L.E., Powell, S.J., Summers, C., Kalsheker, N., Smith, J.C., Markham, A.F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res, 17, pp. 2503-2516
Poloschek, C.M., Kloeckener-Gruissem, B., Hansen, L.L., Bach, M., Berger, W., Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome (2008) Invest Ophthalmol Vis Sci, 49, pp. 4096-4104
Ponjavic, V., Abrahamson, M., Andreasson, S., van Bokhoven, H., Cremers, F.P., Ehinger, B., Fex, G., Phenotype variations within a choroideremia family lacking the entire CHM gene (1995) Ophthalmic Genet, 16, pp. 143-150
Preising, M.N., Ayuso, C., Rab escort protein 1 (REP1) in intracellular traffic: a functional and pathophysiological overview (2004) Ophthalmic Genet, 25, pp. 1001-1010
Preising, M.N., Wegscheider, E., Friedburg, C., Poloschek, C.M., Wabbels, B.K., Lorenz, B., Fundus autofluorescence in carriers of choroideremia and correlation with electrophysiologic and psychophysical data (2009) Ophthalmology, 116, pp. 1201-1209
Pylypenko, O., Rak, A., Reents, R., Niculae, A., Sidorovitch, V., Cioaca, M.D., Bessolitsyna, E., Alexandrov, K., Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase (2003) Mol Cell, 11, pp. 483-494
Rak, A., Pylypenko, O., Niculae, A., Pyatkov, K., Goody, R.S., Alexandrov, K., Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease (2004) Cell, 117, pp. 749-760
Roberts, M.F., Fishman, G.A., Roberts, D.K., Heckenlively, J.R., Weleber, R.G., Anderson, R.J., Grover, S., Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia (2002) Br J Ophthalmol, 86, pp. 658-662
Schwartz, M., Rosenberg, T., van den Hurk, J.A., van de Pol, D.J., Cremers, F.P., Identification of mutations in Danish choroideremia families (1993) Hum Mutat, 2, pp. 43-47
Seabra, M.C., Ho, Y.K., Anant, J.S., Deficient geranylgeranylation of Ram/Rab27 in choroideremia: deficient geranylgeranylation of Ram/Rab 27 in choroideremia (1995) J Biol Chem, 270, pp. 24420-24427
Seabra, M.C., Mules, E.H., Hume, A.N., Rab GTPases, intracellular traffic and disease (2002) Trends Mol Med, 8, pp. 23-30
Sergeev, Y.V., Smaoui, N., Sui, R., Stiles, D., Gordiyenko, N., Strunnikova, N., MacDonald, I.M., The functional effect of pathogenic mutations in Rab escort protein 1 (2009) Mutat Res, 665, pp. 44-50
Stein, M.P., Dong, J., Wandinger-Ness, A., Rab proteins and endocytic trafficking: potential targets for therapeutic intervention (2003) Adv Drug Deliv Rev, 55, pp. 1421-1437
Strunnikova, N.V., Barb, J., Sergeev, Y.V., Thiagarajasubramanian, A., Silvin, C., Munson, P.J., MacDonald, I.M., Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients (2009) PLoS One, 4, pp. e8402
Tanaka, D., Kameyama, K., Okamoto, H., Doi, M., Caenorhabditis elegans Rab escort protein (REP-1) differently regulates each Rab protein function and localization in a tissue-dependent manner (2008) Genes Cells, 13, pp. 1141-1157
van Bokhoven, H., Schwartz, M., Andréasson, S., van den Hurk, J.A., Bogerd, L., Jay, M., Rüther, K., Cremers, F.P., Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients (1994) Hum Mol Genet, 3, pp. 1047-1051
van Bokhoven, H., van den Hurk, J.A., Bogerd, L., Philippe, C., Gilgenkrantz, S., de Jong, P., Ropers, H.H., Cremers, F.P., Cloning and characterization of the human choroideremia gene (1994) Hum Mol Genet, 3, pp. 1041-1046
Ali, B. R., Seabra, M. C., Targeting of Rab GTPases to cellular membranes (2005) Biochem Soc Trans, 33, pp. 652-65
Baron, R. A., Seabra, M., Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate (2008) Biochem J, 415, pp. 67-75
Beaufr re, L., Tuffery, S., Hamel, C., Bareil, C., Arnaud, B., Demaille, J., Claustres, M., The protein truncation test (PTT) as a method of detection for choroideremia mutations (1997) Exp Eye Res, 65, pp. 849-854
Beaufr re, L., Claustres, M., Tuffery, S., No missense mutation in choroideremia patients analyzed to date (1999) Ophthalmic Genet, 20, pp. 89-93
Cremers, F. P., Armstrong, S. A., Seabra, M. C., Brown, M. S., Goldstein, J. L., REP-2, a Rab escort protein encoded by the choroideremia-like gene (1994) J Biol Chem, 269, pp. 2111-2117
Cremers, F. P., van de Pol, D. J., van Kerkhoff, L. P., Wieringa, B., Ropers, H. H., Cloning of a gene that is rearranged in patients with choroideraemia (1990) Nature, 347, pp. 674-677
Garc a-Hoyos, M., Sanz, R., Diego-Alvarez, D., Lorda-S nchez, I., Trujillo-Tiebas, M. J., Cantalapiedra, D., Ramos, C., Ayuso, C., New approach for the refinement of the location of the X-chromosome breakpoint in a previously described female patient with choroideremia carrying a X
Goldberg, A. L., Protein degradation and protection against misfolded or damaged proteins (2003) Nature, 426, pp. 895-899
Guo, Z., Wu, Y. W., Das, D., Delon, C., Cramer, J., Yu, S., Thuns, S., Blankenfeldt, W., Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation (2008) EMBO J, 27, pp. 2444-2456
Lee, T. K., McTaggart, K. E., Sieving, P. A., Heckenlively, J. R., Levin, A. V., Greenberg, J., Weleber, R. G., MacDonald, I. M., Clinical diagnoses that overlap with choroideremia (2003) Can J Ophthalmol, 38, pp. 364-372
Leung, K. F., Baron, R., Seabra, M. C., Thematic review series: lipid posttranslational modifications. Geranylgeranylation of Rab GTPases (2006) J Lipid Res, 47, pp. 467-475
MacDonald, I. M., Mah, D. Y., Ho, Y. K., Lewis, R. A., Seabra, M. C., A practical diagnostic test for choroideremia (1998) Ophthalmology, 105, pp. 1637-1640
MacDonald, I. M., Seabra, M. C., Choroideremia (2006) Principles and practice of clinical electrophysiology of vision, pp. 777-779. , In: Heckenlively JR, Arden GB, editors. 2nd ed. Cambridge: Massachusetts Institute of Technology Press
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res, 17, pp. 2503-2516
Poloschek, C. M., Kloeckener-Gruissem, B., Hansen, L. L., Bach, M., Berger, W., Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome (2008) Invest Ophthalmol Vis Sci, 49, pp. 4096-4104
Preising, M. N., Ayuso, C., Rab escort protein 1 (REP1) in intracellular traffic: a functional and pathophysiological overview (2004) Ophthalmic Genet, 25, pp. 1001-1010
Preising, M. N., Wegscheider, E., Friedburg, C., Poloschek, C. M., Wabbels, B. K., Lorenz, B., Fundus autofluorescence in carriers of choroideremia and correlation with electrophysiologic and psychophysical data (2009) Ophthalmology, 116, pp. 1201-1209
Roberts, M. F., Fishman, G. A., Roberts, D. K., Heckenlively, J. R., Weleber, R. G., Anderson, R. J., Grover, S., Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia (2002) Br J Ophthalmol, 86, pp. 658-662
Seabra, M. C., Ho, Y. K., Anant, J. S., Deficient geranylgeranylation of Ram/Rab27 in choroideremia: deficient geranylgeranylation of Ram/Rab 27 in choroideremia (1995) J Biol Chem, 270, pp. 24420-24427
Seabra, M. C., Mules, E. H., Hume, A. N., Rab GTPases, intracellular traffic and disease (2002) Trends Mol Med, 8, pp. 23-30
Sergeev, Y. V., Smaoui, N., Sui, R., Stiles, D., Gordiyenko, N., Strunnikova, N., MacDonald, I. M., The functional effect of pathogenic mutations in Rab escort protein 1 (2009) Mutat Res, 665, pp. 44-50
Stein, M. P., Dong, J., Wandinger-Ness, A., Rab proteins and endocytic trafficking: potential targets for therapeutic intervention (2003) Adv Drug Deliv Rev, 55, pp. 1421-1437
Strunnikova, N. V., Barb, J., Sergeev, Y. V., Thiagarajasubramanian, A., Silvin, C., Munson, P. J., MacDonald, I. M., Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients (2009) PLoS One, 4, pp. e8402
Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase
Choroideremia (CHM), an X-linked degeneration of the retinal pigmented epithelium (RPE), photoreceptors, and choroid, ultimately leads to blindness. It is caused by loss-of-function of the CHM gene product, the Rab escort protein 1 (REP1) that is involved, together with its homologue REP2, in prenylation of Rab GTPases, key regulators of intracellular vesicular traffic. Here, we report the molecular characterization of 20 unrelated Italian families affected by CHM. We identified 19 different mutations, nine of which are new. In most cases, we analyzed the effect of the mutations at the mRNA level. Furthermore, we demonstrated, by in vitro trancription/translation assays, that the mutated mRNAs produced truncated proteins in all cases but one. In fact, we also identified a novel REP1 missense variant (c.1520A>G; p.H507R) associated to CHM. Thus far, only two other CHM-associated missense mutations have been identified, one of which was a splicing alteration. We investigated the impact of the p.H507R amino acid change on REP1 structure and function, thus providing the first experimental demonstration that correlates a missense mutation in CHM with a functional impairment of REP1. Overall, our results indicate that the REP1-Rab geranyl-geranyl transferase interaction and consequently REP1-mediated Rab prenylation is essential for RPE and photoreceptor function. 32:14601469, 2011. (C) 2011 Wiley Periodicals, Inc.
Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase
Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(357 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(449 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote