Keywords
anticipation
neurological disabilities
neurology
human genetics
mutaciones inestables
anticipación
enfermedades neurológicas
neurología
genética humana
How to Cite
Abstract
Unstable mutations or amplification of DNA tandem repeats sequences constitute a new kind of genetic alteration discovered in the 90´s that cause hereditary diseases. This mutation has been found inside or near important genes involved in the normal neurological function in human beings. In some cases, the presence of the amplification causes altered expression of the genes, their inactivation or the synthesis of a protein with new functions. Some common characteristics of these diseases are that they affect the central nervous system and are degenerative in nature. Most of them show genetic anticipation meaning that the severity of the manifestations increases in each generation and appear at an earlier age. In most cases, the severity of the symptoms is positively correlated with the size of the amplification. Twenty illnesses caused by this kind of mutations have been identified so far. Briefly, this work reviews the current knowledge about this topic.References
Brown, S.A., D. Warburton, L.Y. Brown, C.Y. Yu, E.R. Roeder, S. Stengel-Rutkowski, R.C. Hennekam & M. Muenke. 1998. Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nat. Genet. 20: 180-183.
Buxton, J., P. Shelbourne, J. Davies, C. Jones, T. Van Tongeren, C. Aslanidis, P.de Jong, G. Jansen, M. Anvert, B. Rileyu, R. Williamson & K. Johnson. 1992. Detection of an unstable fragment of DNA specific to individuals with DM. Nature 355: 547-548.
Castro, I. & P. Cuenca. 1987. Tamizaje del sitio frágil en el cromosoma X en una población de retardados mentales. Hallazgos preliminares. Rev. Méd. Hosp. Nal. Niños Costa Rica. 22: 11-14.
Castro, I. & P. Cuenca. 1996. Frecuencia del síndrome del cromosoma X frágil en la Escuela de Enseñanza Especial Fernando Centeno Guell. Acta Ped. Cost. 10: 99-106.
Cuenca, P. & F. Morales. 1999. Mutaciones inestables, causa de algunas enfermedades neurológicas hereditarias. Acta Méd. Cost. 41: 7-15.
Cuenca, P., F. Morales & I. Castro. 2002. Diagnóstico directo de la mutación que causa el síndrome del cromosoma X frágil. Experiencia en Costa Rica. Acta Méd. Cost. 44: 27-33.
Day, J.W., K. Ricker, J.F. Jacobsen, L.J. Rasmussen, K.A. Dick, W. Kress, C. Schneider, M.C. Koch, G.J. Beilman, A.R. Harrison, J.C. Dalton & L.P.W. Ranum. 2003. Myotonic dystrophy type 2. Molecular, diagnostic and clinical spectrum. Neurology 60: 657-664.
De Bacre, E., D. Beysen, C. Oley, B. Lorenz, J. Coequet, P. De Sutter, K. Devriendt, M. Dixon, M. Fellous, J.P. Fryns, A. Garza, C. Jonsrud, P.A. Koivisto, A. Krause, B.P. Leroy, F. Meire, A. Plomp L. Van Maldergem, A. De Paepe, R. Veitia, y L. Messiaen. 2003. FOXL2 and BPES : mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation. Am. J. Hum. Genet. 72: 478-487.
Fu, Y.H., D.P.A Kuhl, A. Pizutti, 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 & 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: 1047-1058.
Grewal, R.P., M. Achari, T. Matsuura, A. Durazo, E. Tayag, L. Zu, S.M. Pulst & T. Ashizawa. 2002. Clinical Features and ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10. Arch. Neurol. 59: 1285-1290.
Holmes, S.E., E. O’Hearn, A. Rosenblatt, C. Callahan, H.S. Hwang, R.G. Ingersoll-Ashworth, A. Fleisher, G. Stevanin, A. Brice, N.T. Potter, C.A. Ross & R.L. Margolis. 2001a. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. Nat. Genet. 29: 377-378.
Holmes, S.E., E. O’Hearn, C.A. Ross & R.L. Margolis. 2001b. SCA12: An unusual mutation leads to an unusual spinocerebellar ataxia. Brain Res. Bull 56: 397-403.
Hsing, A.W, A.P. Chokkalingam, Y.T. Gao, G. Wu, X. Wang, J. Deng, J. Cheng, I.A. Sesterhenn, F.K. Mostofi, T. Chiang, Y.I. Chen, F.Z. Stanczyk & C. Chang. 2002. Polimorphic CAG/CAA repeat length in the AIB1/SRC-3 gene and prostate cancer risk: a population- based case-control study. Cancer Epidemiol. Biomarkers Prev. 11: 337-341.
Langdon, J.A. & J.A. Armour. 2003. Evolution and population genetics of the H-ras minisatellite and cancer predispotition. Hum. Mol. Genet. 15: 891-900.
Lehesjoki, A.E. 2003. Molecular background of progressive myoclonus epilepsy. EMBO. 14: 3473-3478.
Liquori, C.L., K. Ricker, M.L. Moseley, J.F. Jacobsen, W. Kress, S.L. Naylor, J.W. Day & L.P.W. Ranum. 2001. Myotonic Dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 252: 1711- 1714.
Meira-Lima, I.V., J. Zhao, P. Sham, A.C. Pereira, J.F. Krieger & H. Vallada. 2001. Association and linkage studies between bipolar affective disorder and the polymorphic CAG/CTG repeat loci ERDA1, SEF-1B, MAB21L and KCNN3. Mol. Psychiatry 6: 565-569.
Morales, F., P. Cuenca, R. Brian-Gago, M. Sittenfeld-Appel & G. del Valle-Carazo. 2001. Diagnóstico molecular de la distrofia miotónica (DM) en Costa Rica. Acta Méd. Cost. 43: 159-167.
Morales, F., P. Cuenca, G. del Valle, R. Brian, M. Sittenfeld, O. Montoya, T. Ashizawa, A. Rosa & Keith Johnson. 2003. Miotonía congenita: caracterización clínica de una familia costarricense afectada por la enfermedad de Thomsen. Neuroeje 17: 82-86.
Morell, V. 1993. The puzzle of the triple repeats. Science 260: 1422-1423.
Mundlos, S., F. Otto, C. Mundlos, J.B. Mulliken, A.S. Aylsworth, S. Allbright, D. Lindhout, W.G. Cole, W. Henn, J.H. Knoll, M.J. Owen, R. Mertelsmann, B.U. Zabel & B.R. Olsen. 1997. Mutation involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89: 773-779.
Murray, J., H. Cuckle, G. Taylor & J. Hewison,. 1997. Screening for fragile X syndrome: information needs fot health planners. J. Med. Screen. 4: 60-94.
Nolin, S. L., W.T. Brown, A. Glicksman, G.E. Houck Jr., A.D. Gargano, A. Sullivan, V. Biancalana, K. Broendum- Nielsen, H. Hjalgrim, E. Holinsli-Feder, F. Kooy, J. Longshore, J. Macpherson, J.L. Mandel, G. Matthijs, F. Rousseau, P. Steinbach, M.L. Vaeisaenen,
H. vonKoskull & S. Sherman. 2003. Expansion of the Fragile X CGG Repeat in Females with Premutation or Intermediate Alleles. Am. J. Hum. Genet. 72: 454-464.
Oostra, B.A. & R. Willemsem. 2003. A fragile balance: FMR1 expression levels. Hum. Mol. Genet. 12(Review Issue 2): 249-257.
Potaman, V.N., J.J. Bissler, V.I. Hashem, E.A. Oussatcheva, L.L. Luda, S. Shlyakhtenko, Y.L. Lyubchenko, T. Matsuura, T. Ashizawa, M. Leefak, C.J. Benham & R. R. Sinden. 2003. Unpaired structures in SCA 10 (ATTCT)n.(AGAAT)n Repeats. J. Mol. Biol. 326: 1095-1111.
Ranum, L.P.W. & J.W. Day. 2002. Myotonic Dystrophy: clinical and molecular parallels between Myotonic Dystrophy tipe 1 and tipe 2. Curr. Neurol. Neurosc. Reports. 2: 465-470.
Reddy, P.S. & D.E. Housman. 1997. The complex patology of trinucleotide repeats. Curr. Op. Cell. Biol. 9: 364-372.
Sherr, E.H. 2003. The ARX story (epilepsy, mental retardation, autism, and cerebral malformations); one gene leads to many phenotypes. Curr. Opin. Pediatr. 15: 567-571.
Schöls, L., I.Bauer, C. Zühlke, T. Schulte, C. Kölmel, K. Bürk, H. Topka, P. Bauer, H. Przuntek & O. Riess. 2003. Do CTG expansions at the SCA 8 locus cause ataxia? Ann. Neurol. 54: 110-115.
Stevanin, G., H. Fijigasaki, A.S. Lebre, A. Camuzat, C. Jeannequin, C. Dode, J. Takahashi, C. San, R. Bellance, A. Brice & A. Durr. 2003. Huntington’s disease- like phenotype due to trinucleotide repeat expansion in the TBP and JPH3 genes. Brain 126: 1599-1603.
Stromme, P., M.E. Mangelsdorf, M.A. Shaw, K.M. Lower, S.M. Lewis, H. Bruyere, V. Lutcherat, A.K. Gedeon, R.H. Wallace, I.E. Scheffer, G. Turner, M. Partington, S.G. Frints, J.P. Fryns, G.R. Sutherland J.C. Mullcy & J. Geez. 2002. Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat. Genet. 30: 441-445.
Tamimi, R.M., S.E. Hankinson, S. Ding, V. Gagalang, G.P. Larson D. Spiegelman, G.A. Colditz, T.G. Krontiris & D.J. Hunter. 2003. The HRAS1 variable number of tandem repeats and risk of breast cancer. Cancer Epidemiol. Biomarkers Prev. 12: 1528-1530.
Vásquez, M., F. Morales & P. Cuenca. 2003. Aspectos genéticos y moleculares de la enfermedad de Huntington (HD). Neuroeje 17: 74-81.
Weitzel, J.N., S. Ding, G.P. Larson, R.A. Nelson, A. Goodman E.C. Grendys, H.G. Ball & T.G. Krontiris. 2000. The HRAS1 minisatellite locus and risk of ovarian cancer. Cancer Res. 60: 259-261.
Zhang, H., X. Liu, C. Zhang, E. Mudo, F. Macciardi, D.R. Grayson, A.R. Guidotti & J.J. Holden. 2002. Reelin gene alleles and susceptibility to autism spectrum disorders. Mol. Psychiatry. 7: 1012-1017.
REFERENCIAS DE INTERNET
Anónimo, 2004. Online Mendelian Inheritance in man. Johns Hopkins University. Baltimore. (Consultado: 14 de mayo del 2004, http:// www.ncbi.nlm.nih.gov).
Comments
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2004 Revista de Biología Tropical