The molecular basis of fragile X syndrome

Cold Spring Harbor Symposia on Quantitative Biology

Volumn 61, Issue , 1996, Pages 679-687

  Eberhart, D E ^a   Warren, S T ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GENE PRODUCT; MESSENGER RNA; RNA BINDING PROTEIN; FRAGILE X MENTAL RETARDATION PROTEIN;

CHROMOSOME XQ; CONFERENCE PAPER; FRAGILE X SYNDROME; HUMAN; MENTAL DEFICIENCY; METHYLATION; MOLECULAR CLONING; PRIORITY JOURNAL; RIBOSOME; TRINUCLEOTIDE REPEAT; ARTICLE; CEREBELLUM; CHROMATIN; CLINICAL FEATURE; CONFORMATION; DNA METHYLATION; GENE EXPRESSION; GENE STRUCTURE; HIPPOCAMPUS; INHERITANCE; NONHUMAN; PATHOGENESIS; PROTEIN FUNCTION;

EID: 0030428905     PISSN: 00917451     EISSN: None     Source Type: Book Series    
DOI: 10.1101/sqb.1996.061.01.068     Document Type: Conference Paper

References (74)

1. Abitbol, M., C. Menini, A.-L. Delezoide, T. Rhyner, M. Vekemans, and J. Mallet. 1993. Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat. Genet. 4: 147.
2. Antequera, F., J. Boyes, and A. Bird. 1990. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell 62: 503.
3. Ashley, C.T. and S.T. Warren. 1995. Trinucleotide repeat expansion and human disease. Annu. Rev. Genet. 29: 703.
4. Ashley, C.T., K.D. Wilkinson, D. Reines, and S.T. Warren. 1993a. FMR1 protein: Conserved RNP family domains and selective RNA binding. Science 262: 563.
5. Ashley, C.T., J.S. Sutcliffe, C.B. Kunst, H.A. Leiner, E.E. Eichler, D.L. Nelson, and S.T. Warren. 1993b. Human and murine FMR-1: Alternative splicing and translational initiation downstream of the CGG repeat. Nat. Genet. 4: 244.
6. Boyes, J. and A. Bird. 1991. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64: 1123.
7. Campuzano, V., L. Montermini, M.D. Molto, L. Pianese, M. Cossee, F. Cavalcanti, E. Monros, F. Rodius, F. Duclos, A. Monticelli, F. Zara, J. Canizares, H. Koutnikova, S.I. Bidichandani, C. Gellera, A. Brice, P. Trouillas, G.D. Michele, A. Filla, R.D. Frutos, F. Palau, P.I. Patel, S.D. Donato, J.-L. Mandel, S. Cocozza, M. Koenig, and M. Pandolfo. 1996. Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271: 1423.
8. Coy, J.F., Z. Sedlacek, D. Bachner, H. Hameister, S. Joos, P. Lichter, H. Delius, and A. Poustka. 1995. Highly conserved 3′ UTR and expression pattern of FXR1 points to a divergent gene regulation of FXR1 and FMR1. Hum. Mol. Genet. 4: 2209.
9. De Boulle, K., A.J.M.H. Verkerk, E. Reyniers, L. Vits, J. Hendrickx, B. Van Roy, F. Van den Bos, E. de Graaff, B.A. Oostra, and P.J. Willems. 1993. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat. Genet. 3: 31.
10. Devys, D., Y. Lutz, N. Rouyer, J.-P. Bellocq, and J.-L. Mandel. 1993. The FMR-1 protein is cytoplasmic, most abundant in neurons, and appears normal in carriers of the fragile X premutation. Nat. Genet. 4: 335.
11. Dutch-Belgian Fragile X Consortium. 1994. FMR1 knockout mice: A model to study fragile X mental retardation. Cell 78: 23.
12. Eberhart, D.E., H.E. Malter, Y. Feng, and S.T. Warren. 1996. The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum. Mol. Genet. 5: 1083.
13. Eichler, E.E., S. Richards, R.A. Gibbs, and D.L. Nelson. 1993. Fine structure of the human FMR1 gene. Hum. Mol. Genet. 2: 1147.
14. Eichler, E.E., C.B. Kunst, K.A. Lugenbeel, O.A. Ryder, D. Davison, S.T. Warren, and D.L. Nelson. 1995. Evolution of the cryptic FMR1 CGG repeat. Nat. Genet. 11: 301.
15. Eichler, E.E., J.J.A. Holden, B.W. Popovich, A.L. Reiss, K. Snow, S.N. Thibodeau, C.S. Richards, P.A. Ward, and D.L. Nelson. 1994. Length of uninterrupted CGG repeats determines instability in the FMR1 gene. Nat. Genet. 8: 88.
16. Feng, Y., F. Zhang, L.K. Lokey, J.L. Chastain, L. Lakkis, D. Eberhart, and S.T. Warren. 1995. Translational suppression by trinucleotide repeat expansion at FMR1. Science 268: 731.
17. Fischer, U., J. Huber, W.C. Boelens, I.W. Mattaj, and R. Luhrmann. 1995. The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82: 475.
18. Frey, S., C Schweigert, M. Krug, and B. Lossner. 1991. Long-term potentiation induced changes in protein synthesis of hippocampal subfields of freely moving rats: Time-course. Biomed. Biochim. Acta 50: 1231.
19. Fu, Y.-H., D.P. Kuhl, A. Pizzuti, M. Pieretti, J.S. Sutcliffe, S. Richards, A.J.M.H. Verkerk, J.J.A. Holden, R.G. Fenwick Jr., S.T. Warren, B.A. Oostra, D.L. Nelson, and C.T. Caskey. 1991. Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell 67: 1047.
20. Gacy, A.M., G. Goellner, N. Juranic, S. Macura, and C.T. McMurray. 1995. Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell 81: 533.
21. Gerace, L. 1995. Nuclear export signals and the fast track to the cytoplasm. Cell 82: 341.
22. Gorlich, D. and I. Mattaj. 1996. Nucleocytoplasmic transport. Science 271: 1513.
23. Hansen, R.S., T.K. Canfield, M.M. Lamb, S.M. Gartler, and C.D. Laird. 1993. Association of fragile X syndrome with delayed replication of the FMR1 gene. Cell 73: 1403.
24. Hergersberg, M., K. Matsuo, M. Gassman, W. Schaffner, B. Luscher, T. Rulicke, and A. Aguzzi. 1995. Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice. Hum. Mol. Genet. 4: 359.
25. Hinds, H.L., C.T. Ashley, D.L. Nelson, S.T. Warren, D.E. Housman, and M. Schalling. 1993. Tissue specific expression of FMR1 provides evidence for a functional role in fragile X syndrome. Nat. Genet. 3: 36.
26. Hirst, M.C., P.K. Grewal, and K.E. Davies. 1994. Precursor arrays for triplet repeat expansion at the fragile X locus. Hum. Mol. Genet. 3: 1553.
27. Hirst, M., P. Grewal, A. Flannery, R. Slatter, E. Maher, D. Barton, J.-P. Fryns, and K. Davies. 1995. Two new cases of FMR1 deletions associated with mental impairment. Am. J. Hum. Genet. 56: 67.
28. Hornstra, I.K., D.L. Nelson, S.T. Warren, and T.P. Yang. 1993. High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome. Hum. Mol. Genet. 2: 1659.
29. Jacobs, P.A., H. Bullman, J. Macpherson, S. Youings, V. Rooney, A. Watson, and N.R. Dennis. 1993. Population studies of the fragile X: A molecular approach. J. Med. Genet. 30: 454.
30. Khandjian, E.W., F. Corbin, S. Woerly, and F. Rousseau. 1996. The fragile X mental retardation protein is associated with ribosomes. Nat. Genet. 12: 91.
31. Khandjian, E.W., A. Fortin, A. Thibodeau, S. Tremblay, F. Cote, D. Devys, J.-L. Mandel, and F. Rousseau. 1995. A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and modulated in cell culture. Hum. Mol. Genet. 4: 783.
32. Kirchgessner, C.U., S.T. Warren, and H.L. Willard. 1995. X inactivation of the FMR1 fragile X mental retardation gene. J. Med. Genet. 32: 925.
33. Kremer, E.J., M. Pritchard, M. Lynch, S. Yu, K. Holman, E. Baker, S.T. Warren, D. Schlessinger, G.R. Sutherland, and R.I. Richards. 1991. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CGG)n. Science 252: 1711.
34. Kunst, C.B. and S.T. Warren. 1994. Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles. Cell 77: 853.
35. Loesch, D.Z., R. Huggins, D.A. Hay, A.K. Gedeon, J.C. Mulley, and G.R. Sutherland. 1993. Genotype-phenotype relationships in fragile X syndrome: A family study. Am. J. Hum. Genet. 53: 1064.
36. Lugenbeel, K.A., A.M. Peier, N.L. Carson, A.E. Chudley, and D.L. Nelson. 1995. Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nat. Genet. 10: 483.
37. McConkie-Rosell, A., A.M. Lachiewicz, G.A. Spiridigliozzi, J. Tarleton, S. Schoenwald, M.C. Phelan, P. Goonewardena, X. Ding, and W.T. Brown. 1993. Evidence that methylation of the FMR-1 locus is responsible for variable phenotypic expression of the fragile X syndrome. Am. J. Hum. Genet. 53: 800.
38. Michael, W.M., M. Choi, and G. Dreyfuss. 1995. A nuclear export signal in hnRNP A1: A signal-mediated, temperature-dependent nuclear protein export pathway. Cell 83: 291.
39. Miyashiro, K., M. Dichter, and J. Eberwine. 1994. On the nature and differential distribution of mRNAs in hippocampal neurites: Implications for neuronal functioning. Proc. Natl. Acad Sci. 91: 10800.
40. Musco, G., G. Stier, C. Joseph, M. Antonietta, C. Morelli, M. Nilges, T.J. Gibson, and A. Pastore. 1996. Three-dimensional structure and stability of the KH domain: Molecular insights into the fragile X syndrome. Cell 85: 237.
41. Oberlé, I., F. Rousseau, D. Heitz, C. Kretz, D. Devys, A. Hanauer, J. Boué, M.F. Bertheas, and J.-L. Mandel. 1991. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252: 1097.
42. Pieretti, M., F. Zhang, Y.H. Fu, S.T. Warren, B.A. Oostra, C.T. Caskey, and D.L. Nelson. 1991. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66: 817.
43. Price, D.K., F. Zhang, C.T. Ashley, and S.T. Warren. 1996. The chicken FMR1 gene is highly conserved with a CCT 5′ untranslated repeat and encodes an RNA-binding protein. Genomics 31: 3.
44. Reyniers, E., L. Vits, K. De Boulle, B. Van Roy, D. Van Velzen, E. de Graaff, A.J.M.H. Verkerk, H.Z.J. Jorens, J.K. Darby, B. Oostra, and P.J. Willems. 1993. The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Nat. Genet. 4: 143.
45. Richards, R. I. 1994. Simple repeat DNA is not replicated simply. Nat. Genet. 6: 114.
46. Richards, R.I., K. Holman, and G.R. Sutherland. 1993. Fragile X syndrome unstable element, p(CCG)n, and other simple tandem repeats sequences are binding sites for specific nuclear proteins. Hum. Mol. Genet. 2: 1429.
47. Richards, R.I., K. Holman, K. Friend, E. Kremer, D. Hillen, A. Staples, W.T. Brown, P. Goonewardena, J. Tarleton, C. Schwartz, and G.R. Sutherland. 1992. Evidence of founder chromosomes in fragile X syndrome. Nat. Genet. 1: 257.
48. Riggins, G.J., L.K. Lokey, J.L. Chastain, H.A. Leiner, S.L. Sherman, K.D. Wilkinson, and S.T. Warren. 1992. Human genes containing polymorphic trinucleotide repeats. Nat. Genet. 2: 186.
49. Rousseau, F., D. Heitz, V. Biancalana, S. Blumenfield, C. Kretz, J. Boué, N. Tommerup, C. van der Hagen, C. DeLozier-Blanchet, M.F. Croquette, S. Gilgenkrantz, P. Jalbert, M.A. Voelckel, T. Oberlé, and J.-L. Mandel. 1991. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N. Engl. J. Med. 325: 1673.
50. Schalling, M., T.J. Hudson, K.H. Buetow, and D.E. Housman. 1993. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat. Genet. 4: 135.
51. Sherman, S.L., N.E. Morton, P.A. Jacobs, and G. Turner. 1984. The marker (X) syndrome: A cytogenetic and genetic analysis. Ann. Hum. Genet. 48: 21.
52. Sherman, S.L., P.A. Jacobs, N.E. Morton, U. Froster-Iskenius, P.N. Howard-Peebles, K.B. Nielson, M.W. Partington, G.R. Sutherland, G. Turner, and M. Watson. 1985. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum. Genet. 69: 289.
53. Siomi, H., M.C. Siomi, R.L. Nussbaum, and G. Dreyfuss. 1993. The protein product of the fragile X gene, FMR1, has characteristics of an RNA binding protein. Cell 74: 291.
54. Siomi, H., M. Choi, M.C. Siomi, R.L. Nussbaum, and G. Dreyfuss. 1994. Essential role for KH domains in RNA binding: Impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. Cell 77: 33.
55. Siomi, M., H. Siomi, W.H. Sauer, S. Srinivasan, R.L. Nussbaum, and G. Dreyfuss. 1995. FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J. 14: 2401.
56. Smits, A.P.T., J.C.F.M. Dreesen, J.G. Post, D.F.C.M. Smeets, C. de Die-Smulders, T. Spaans-van der Bijl, L.C.P. Govaerts, S.T. Warren, B.A. Oostra, and B.A. van Oost. 1993. The fragile X syndrome: No evidence for any recent mutations. J. Med. Genet. 30: 94.
57. Snow, K., D.J. Tester, K.E. Kruckeberg, D.J. Schaid, and S.N. Thibodeau. 1994. Sequence analysis of the fragile X trinucleotide repeat: Implications for the origin of the fragile X mutation. Hum. Mol. Genet. 3: 1543.
58. Snow, K., L.K. Doud, R. Hagerman, R.G. Pergolizzi, S.H. Erster, and S.N. Thibodeau. 1993. Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population. Am. J. Hum. Genet. 53: 1217.
59. Steward, O. 1994. Dendrites as compartments for macromolecular synthesis. Proc. Natl. Acad. Sci. USA 91: 10766.
60. Sutcliffe, J.S., D.L. Nelson, F. Zhang, M. Pieretti, C.T. Caskey, D. Saxe, and S.T. Warren. 1992. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1: 397.
61. Tamanini, F., N. Meijer, C. Verheij, P.J. Willems, H. Galjaard, B.A. Oostra, and A.T. Hoogeveen. 1996. FMRP is associated to the ribosomes via RNA. Hum. Mol. Genet. 5: 801.
62. Verheij, C., C.E. Bakker, E. de Graaff, J. Keulemans, R. Willemsen, A.J.M.H. Verkerk, H. Galjaard, A.J.J. Reuser, A.T. Hoogeveen, and B.A. Oostra. 1993. Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature 363: 722.
63. Verheij, C., E. de Graaff, C.E. Bakker, R. Willemsen, P.J. Willems, N. Meijer, H. Galjaard, A.J.J. Reuser, B.A. Oostra, and A.T. Hoogeveen. 1995. Characterization of FMR1 proteins isolated from different tissues. Hum. Mol. Genet. 4: 895.
64. Verkerk, A.J.M.H., M. Pieretti, J.S. Sutcliffe, Y.-H. Fu, D.P.A. Kuhl, A. Pizutti, O. Reiner, S. Richards, M.F. Victoria, F. Zhang, B.E. Eussen, G.J.B. van Ommen, L.A.J. Blonden, G.J. Riggins, J.L. Chastain, C.B. Kunst, H. Galjaard, C.T. Caskey, D.L. Nelson, B.A. Oostra, and S.T. Warren. 1991. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65: 905.
65. Visa, N., A.T. Alzhanova-Ericsson, X. Sun, E. Kiseleva, B. Bjorkroth, T. Wurtz, and B. Daneholt. 1996. A premRNA-binding protein accompanies the RNA from the gene through the nuclear pores and into polysomes. Cell 84: 253.
66. Wang, Y.-H. and J. Griffith. 1995. Expanded CTG triplet blocks from the myotonic dystrophy gene create the strongest known natural nucleosome positioning elements. Genomics 25: 570.
67. Wang, Y.-H., S. Amirhaeri, S. Kang, R.D. Wells, and J.D. Griffith. 1994. Preferential nucleosome assembly at the DNA triplet repeat from the myotonic dystrophy gene. Science 265: 669.
68. Warren, S.T. 1996. The expanding world of trinucleotide repeats. Science 271: 1374.
69. Warren, S.T. and C.T. Ashley. 1995. Triplet repeat expansion mutations: The example of fragile X syndrome. Annu. Rev. Neurosci. 18: 77.
70. Warren, S.T. and D.L. Nelson. 1994. Advances in molecular analysis of fragile X syndrome. J. Am Med. Assoc. 271: 536.
71. Wen, W., J.L. Meinkoth, R.Y. Tsien, and S.S. Taylor. 1995. Identification of a signal for rapid export of proteins from the nucleus. Cell 82: 463.
72. Wohrle, D., I. Hennig, W. Vogel, and P. Steinbach. 1993. Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat. Genet. 4: 140.
73. Yu, S., M. Pritchard, E. Kremer, M. Lynch, J. Nancarrow, E. Baker, K. Holman, J.C. Mulley, S.T. Warren, D. Schlessinger, G.R. Sutherland, and R.I. Richards. 1991. Fragile X genotype characterized by an unstable region of DNA. Science 252: 1179.
74. Zhang, Y., J.P. O'Connor, M.C. Siomi, S. Srinivasan, A. Dutra, R.L. Nussbaum, and G. Dreyfuss. 1995. The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J. 14: 5358.