Fragile-X syndrome and myotonic dystrophy: Parallels and paradoxes

Current Opinion in Genetics and Development

Volumn 8, Issue 2, 1998, Pages 245-253

  Tapscott, Stephen J ^a   Klesert, Todd R ^a   Widrow, Rj ^a   Stöger, Reinhard ^a   Laird, Charles D ^a  

^a Fred Hutchinson Cancer Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CPG ISLAND; DNA METHYLATION; ETIOLOGY; FRAGILE X SYNDROME; GENETIC TRANSCRIPTION; HUMAN; MYOTONIC DYSTROPHY; NUCLEOTIDE REPEAT; PRIORITY JOURNAL;

EID: 0032055011     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80148-2     Document Type: Article

References (107)

1. Reddy PS, Housman DE. The complex pathology of trinucleotide repeats. Curr Opin Cell Biol. 9:1997;364-372.
2. Merenstein SA, Sobesky WE, Taylor AK, Riddle JE, Tran HX, Hagerman RJ. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet. 64:1996;388-394.
3. Stöger R, Kajimura TM, Brown WT, Laird CD. Epigenetic variation illustrated by DNA methylation patterns of the fragile-X gene FMR1. of special interest Hum Mol Genet. 6:1997;1791-1801 Detailed patterns were obtained for cytosine methylation within a 200 bp region of the CpG island of FMR1, using the bisulfite-conversion and PCR sequencing method of Clark and Frommer. 'Epigenotypes' were obtained for normal alleles and for expanded alleles from methylation-mosaic males of a family having five fragile-X sons with a broad range of phenotypes. Clinical implications are presented concerning the use of Eagl (100% reliable as an indicator of hypermethylation) and the nature of mosaicism (the proportion of alleles showing hypo- and hypermethylation), as well as more general implications for the nature of cytosine methylation in leukocytes.
4. Hwu WL, Wang TR, Lee YM. FMR1 enhancer is regulated by cAMP through a cAMP-responsive element. of special interest DNA Cell Biol. 6:1997;449-453 DNAse I footprinting was used to define a 22 bp region within the FMR1 promoter. This region was protected by nuclear factor(s), which binding was greatly reduced by cytosine methylation in CpG dinucleotides. Transfection assays with this 22 bp sequence demonstrated methylation-sensitive enhancer activity, with stimulation by 'cAMP-responsive element binding protein' and forskolin also being reported. Enhancer activity was abolished by point mutations, indicating a key role for this 22 bp element in cAMP-dependent regulation of PMR1 transcription.
5. Schwemmle S, de Graaff E, Deissler H, Glaser D, Wohrle D, Kennerknecht I, Just W, Oostra BA, Dorfler W, Vogel W, Steinbach P. Characterization of FMR1 promoter elements by in vivo footprinting analysis. of special interest Am J Hum Genet. 60:1997;1354-1362 In vivo DNA footprinting analysis demonstrated four protein binding sites in the unmethylated promoter of active FMR1 alleles; no footprints were observed in the methylated promoters of inactive alleles. The authors suggest that transcriptional silencing by methylation results from lack of transcription factor binding.
6. Eberhart DE, Warren ST. Nuclease sensitivity of permeabilized cells confirms altered chromatin formation at the fragile X locus. Somatic Cell Mol Genet. 22:1996;435-441.
7. Wen GY, Jenkins EC, Yao XL, Yoon D, Brown WT, Wisniewski HM. Transmission electron microscopy of chromosomes by longitudinal section preparation: application to fragile X chromosome analysis. of special interest Am J Med Genet. 68:1997;445-449 Transmission electron microscopy of sections of a fragile-X chromosome suggest the possibility that chromatin at the FRAXA site may be hyper- rather than hypocondensed.
8. Harrison CJ, Jack EM, Allen TD, Harris R. The fragile X: a scanning electron microscope study. J Med Genet. 20:1983;280-285.
9. Sherman SL, Jacobs PA, Morton NE, Froster-Iskenius U, Howard-Peebles PN, Nielsen KB, Partington MW, Sutherland GR, Turner G, Watson M. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet. 9:1985;289-299.
10. Butler MG, Brunschwig A, Miller LK, Hagerman RJ. Standards for selected anthropometric measurements in males with the fragile X syndrome. Pediatrics. 89:1992;1059-1062.
11. Eberhart DE, Feng Y, Warren ST. Identification of a cytoplasmic anchor domain responsible for the subcellular localization of the fragile X mental retardation protein, FMRP. Am J Hum Genet. 7:1995;A39.
12. Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. of special interest J Neurosci. 17:1997;1539-1547 Biochemical and immunocytochemical assays indicate that FMR1 protein has a role in the translation of proteins involved in dendritic structure or function.
13. Weiler IJ, Irwin SA, Klintsova AY, Spencer CM, Brazelton AD, Miyashiro K, Comery TA, Patel B, Eberwine J, Greenough WT. Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. of special interest Proc Natl Acad Sci USA. 94:1997;5395-5400 Translation of FMR1 mRNA increases in sub-cellular fractions after stimulation of metabotropic glutamate receptors, suggesting that rapid translation of FMR1 protein occurs in response to synapse activation. The authors propose that this synapse-induced synthesis and activity of FMR1 protein are important for the normal maturation of synaptic connections.
14. Pembrey ME, Winter R, Davies K. A premutation that generates a defect at crossing over explains the inheritance of fragile-X mental retardation. Am J Med Genet. 21:1985;709-717.
15. Laird CD: Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation. Genetics 117:587-599.
16. Laird C, Jaffe E, Karpen G, Lamb M, Nelson R. Fragile sites in human chromosomes as regions of late-replicating DNA. Trends Genet. 3:1987;274-281.
17. Zheng CJ, Byers B, Moolgavkar SH. Allelic instability in mitosis: a unified model for dominant disorders. Proc Natl Acad Sci USA. 90:1993;10178-10182.
18. Yu S, Mulley J, Loesch D, Turner G, Donnelly A, Gedeon G, Hillen D, Kremer E, Lynch M, Pritchard M, Sutherland GR, et al. Fragile-X syndrome: unique genetics of the heritable unstable element. Am J Hum Genet. 50:1992;968-980.
19. Fu Y-H, Kuhl DPA, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJMH, Holden JJA, Fenwick RG Jr, Warren ST, et al. Variation of the CGG repeat at the Fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 67:1991;1047-1058.
20. Murray A, Macpherson JN, Pound MC, Sharrock A, Youings SA, Dennis NR, McKechnie N, Linehan P, Morton NE, Jacobs PA. The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission. of special interest Hum Mol Genet. 6:1997;173-184 The stability of expanded trinucleotide repeats at FRAXA or FRAXE was studied in 139 families; four X-linked microsatellite loci were also examined. Although no correlation was observed between haplotype and the probability of expansion of FRAXA premutations, instabilities at both FRAXA and FRAXE were sometimes observed in conjunction with a second instability at a microsatellite locus, suggesting that general genomic instability is one mechanism by which triplet-repeat expansions arise.
21. Wohrle D, Hirst MC, Kennerknecht I, Davies KE, Steinbach P. Genotype mosaicism in fragile X fetal tissues. Hum Genet. 89:1992;114-116.
22. Moutou C, Vincent MC, Biancalana V, Mandel JL. Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic. of special interest Hum Mol Genet. 6:1997;971-979 This carefully reasoned paper argues that the transition from unmethylated moderate-size expansions (premutations) to methylated large expansions (full mutations) occurs either pre-zygotically, or very soon after fertilization (before day 3). The analysis is based on data for expansions and methylation in fetal tissues, mother-offspring changes in CGG repeat size, and mathematical simulations. The authors also suggest that the absence of full mutations in sperm of affected males is explained by selective growth of spermatogonial cells that have undergone loss of methylation and reduction in size of the expanded CGG repeats.
23. Auerbach C. A possible case of delayed mutation in man. Ann Hum Genet. 20:1956;266-268.
24. Chandra H, Brown S. Chromosome imprinting and the mammalian X chromosome. Nature. 253:1975;165-168.
25. Hansen RS, Canfield TK, Lamb MM, Gartler SM, Laird CD. Association of fragile-X syndrome with delayed replication of the FMR1 gene. Cell. 73:1993;1403-1409.
26. Hansen RS, Canfield TK, Fjeld AD, Mumm S, Laird CD, Gartler SM. A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication. of special interest Proc Natl Acad Sci USA. 94:1997;4587-4592 The delayed replication domain that includes FMR1 in fragile-X individuals with large, methylated CGG expansions was characterized. The boundaries of this domain can extend at least 400 kb 5′, and 600 kb 3′ of FMR1, suggesting the variable involvement of multiple replicons in delayed replication. This domain may provide a model for the spread of inactivation.
27. Malter HE, Iber JC, Willemsen R, de Graaff E, Tarleton JC, Leisti J, Warren ST, Oostra BA. Characterization of the full fragile X syndrome mutation in fetal gametes. of special interest Nat Genet. 15:1997;165-169 Analysis of ovaries of fetuses carrying full mutations in somatic cells indicates that large but unmethylated expansions are present in oocytes. DNA and protein studies of two testes from 13 week and 17 week fetuses with somatic full mutations are consistent with the hypothesis that the male germline begins with full mutations, but that cells with contracted and unmethylated CGG repeats grow selectively to provide only premutation sperm.
28. Webb TP, Bundey S, Thake K, Todd J. The frequency of the fragile X chromosome among schoolchildren in Coventry. J Med Genet. 23:1986;396-399.
29. Morton JE, Bundey S, Webb TP, MacDonald F, Rindl PM, Bullock S. Fragile X syndrome is less common than previously estimated. of special interest J Med Genet. 34:1997;1-5 A pivotal 1986 study reported a high prevalence of about 1/1000 for the fragile-X syndrome among school children in Coventry, England. Individuals previously diagnosed with fragile-X syndrome have now been re-evaluated using molecular tests for the expanded, hypermethylated CGG repeat. Based on the new molecular diagnostic data, revised prevalence estimates for this study population are now 3 to 6 fold lower than previously reported, approached the 1/6000 estimates of de Vries et al. [30].
30. de Vries BB, van den Ouweland AM, Mohkamsing S, Duivenvoorden HJ, Mol E, Gelsema K, van Rijn M, Halley DJ, Sandkuijl LA, Oostra BA, et al. Screening and diagnosis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. of special interest Collaborative Fragile X Study Group, Am J Hum Genet. 61:1997;660-667 Using DNA tests, a screening for fragile-X syndrome in the southwestern Netherlands provided a prevalence estimate of about 1 per 6000 males.
31. Falik-Zaccai TC, Shachak E, Yalon M, Lis Z, Borochowitz Z, Macpherson JN, Nelson DL, Eichler EE. Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype. Am J Hum Genet. 60:1997;103-112.
32. Rousseau F, Heitz D, Biancalana V, Blumenfeld S, Kretz C, BouÄ J, Tommerup N, Van Der Hagen C, De Lozier-Blanchet C, Croquette M-F, et al. Direct diagnosis by DNA analysis of the fragile-X syndrome of mental retardation. N Engl J Med. 325:1991;1673-1681.
33. Pieretti M, Zhang F, Fu Y-H, Warren ST, Oostra BA, Caskey CT, Nelson DL. Absence of expression of the FMR-1 gene in Fragile X syndrome. Cell. 66:1991;817-822.
34. Feng Y, Zhang F, Lokey LK, Chastain JL, Lakkis L, Eberhart D, Warren ST. Translational suppression by trinucleotide repeat expansion at FMR1. Science. 268:1995;731-734.
35. de Vries BB, Jansen CC, Duits AA, Verheij C, Willemsen R, van Hemel JO, van den Ouweland AM, Niermeijer MF, Oostra BA, Halley DJ. Variable FMR1 gene methylation of large expansions leads to variable phenotype in three males from one fragile X family. J Med Genet. 33:1996;1007-1010.
36. Willemsen R, Smits A, Mohkamsing S, van Beerendonk H, de Haan A, de Vries B, van den Ouweland A, Sistermans E, Galjaard H, Oostra BA. Rapid antibody test for diagnosing fragile X syndrome: a validation of the technique. of special interest Hum Genet. 99:1997;308-311 A new diagnostic approach to fragile-X syndrome is proposed. Anti-FMR1 antibody was used to test uncultured cells from amniotic fluid for expression of FMR1; striking differences between a normal and a fragile-X fetus were presented.
37. Maddalena A, Yadvish KN, Spence WC, Howard-Peebles PN. A fragile X mosaic male with a cryptic full mutation detected in epithelium but not in blood. Am J Med Genet. 64:1996;309-312.
38. Dobkin CS, Nolin SL, Cohen I, Sudhalter V, Bialer MG, Ding XH, Jenkins EC, Zhong N, Brown WT. Tissue differences in fragile X mosaics: mosaicism in blood cells may differ greatly from skin. Am J Med Genet. 64:1996;296-301.
39. Brook JDMC, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. [published erratum appears in Cell 1992, 69:385] Cell. 68:1992;799-808.
40. Hunter A, Tsilfidis C, Mettler G, Jacob P, Mahadevan M, Surh L, Korneluk R. The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy. J Med Genet. 29:1992;774-779.
41. Reardon W, Harley HG, Brook JD, Rundle SA, Crow S, Harper PS, Shaw DJ. Minimal expression of myotonic dystrophy: a clinical and molecular analysis. J Med Genet. 29:1993;770-773.
42. Harley HG, Brook JD, Rundle SA, Crow S, Reardon W, Buckler AJ, Harper PS, Housman DE, Shaw D. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. [see comments] Nature. 355:1992;545-546.
43. Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barcelo J, O'Hoy K, et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science. 255:1992;1253-1255.
44. Gennarelli M, Novelli G, Andreasi Bassi F, Martorell L, Cornet M, Menegazzo E, Mostacciuolo ML, Martinez JM, Angelini C, Pizzuti A, et al. Prediction of myotonic dystrophy clinical severity based on the number of intragenic [CTG]n trinucleotide repeats. Am J Med Genet. 65:1996;342-347.
45. Wong LJ, Axhizawa T, Monckton DG, Caskey CT, Richards CS. Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size dependent. Am J Hum Genet. 56:1995;114-122.
46. Thornton CAJ. Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes. Ann Neurol. 35:1994;104-107.
47. Monckton DG, Caskey CT. Unstable triplet repeat diseases. Circulation. 91:1995;513-519.
48. Massari A, Generalli M, Menegazzo E, Pizzuti A, Silani V, Mastrogiacomo I, Pagani E, Angelini C, Scarlato G, Novelli G, et al. Postzygotic instability of the myotonic dystrophy p[AGC] repeat supported by larger expansions in muscle and reduced amplifications in sperm. J Neurol. 242:1995;379-383.
49. Martorell L, Johnson K, Boucher CA, Baiget M. Somatic instability of the myotonic dystrophy (CTG)n repeat during human fetal development. of special interest Hum Mol Genet. 6:1997;877-880 This study investigated the somatic instability of the myotonic dystrophy CTG repeat in human fetuses. The maximum instability is between gestational weeks 13 and 16, and shows tissue specificity.
50. Martorell L, Martinez JM, Carey N, Johnson K, Baiget M. Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period. J Med Genet. 32:1995;593-596.
51. Kang S, Jaworski A, Ohshima K, Wells RD. Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli. Nat Genet. 10:1995;213-218.
52. Freudenreich CH, Stavenhagen JB, Zakian VA. Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome. of special interest Mol Cell Biol. 17:1997;2090-2098 CTG tract replication in yeast was used to show that repeat orientation relative to DNA replication influenced instability, supporting a model of hairpin- polymerase slippage that had been previously proposed.
53. Samadashwily GM, Raca G, Mirkin SM. Trinucleotide repeats affect DNA replication in vivo. of special interest Nat Genet. 17:1997;298-304 CTG and CGG repeats in bacterial DNA induced stalling of the replication tork within the repeat sequence that depended both on repeat length and orientation relative to the replication origin. These results suggest that secondary structure of the lagging strand template may interfere with normal repeat replication.
54. Carango P, Noble JE, Marks HG, Funanage VL. Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy. Genomics. 18:1993;340-348.
55. Fu Y-H, Friedman DL, Richards S, Pearlman JA, Gibbs RA, Pizzuli A, Ashizawa T, Perryman MP, Scarlato G, Fenwick RG Jr, Caskey CT. Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science. 260:1993;235-238.
56. Novelli G, Generalli M, Zelano G, Pizzuti A, Fattorini C, Caskey CT, Dallapicolla B. Failure in detecting mRNA transcripts from the mutated allele in myotonic dystrophy muscle. Biochem Mol Biol Int. 29:1993;291-297.
57. Hofmann-Radvanyi H, Lavedan C, Rabes J-P, Savoy D, Duros C, Johnson K, Junien C. Myotonic dystrophy: absence of CTG enlarged transcript in congenital forms, and low expression of normal allele. Hum Molec Genet. 2:1993;1263-1266.
58. Laurent A, Costa JM, Assouline B, Voyer M, Vidaud M. Myotonic dystrophy protein kinasse gene expression in skeletal muscle from congenitally affected infants. Ann Genet. 40:1997;169-174.
59. Sabouri LA, Mahadevan MS, Narang M, Lee DS, Surh LC, Kroneluk RG. Effect of myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. Nat Genet. 4:1993;233-238.
60. Bhagwati S, Ghatpande A, Leung B. Normal levels of DM RNA and myotonin protein kinase in skeletal muscle from adult myotonic dystrophy (DM) patients. Biochimica et Biophysica Acta. 1317:1996;155-157.
61. Taneja KL, McCurrach M, Schalling M, Housman D, Singer RH. Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J Cell Biol. 128:1995;995-1002.
62. Hamshere MG, Newman EE, Alwazzan M, Athwal BS, Brook JD. Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. of special interest Proc Natl Acad Sci USA. 94:1997;7394-7399 Demonstrated nuclear retention and decreased poly-adenylation of transcripts from a DMPK allele with a CTG expansion. This study did not find significant differences in expression of the 59 or DMAHP genes.
63. Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE. Expansion of a CUG trinucleotide repeat in the 3′ untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. of special interest Proc Natl Acad Sci USA. 94:1997;7388-7393 Transcripts of the DMPK gene with CTG expansion were shown to form stable intranuclear clusters that are tightly associated with the nuclear matrix. This dramatic demonstration of abnormal DMPK RNA processing suggests a novel function of the RNA CUG repeat.
64. Wang J, Pegoraro E, Menegazzo E, Gennarelli M, Hoop RC, Angelini C, Hoffman EP. Myotonic dystrophy: evidence for a possible dominant-negative RNA mutation. Hum Mol Genet. 4:1995;599-606.
65. Krahe R, Ashizawa T, Abbruzzese C, Roeder E, Carango P, Giacanelli M, Funanage VL, Siciliano MJ. Effect of myotonic dystrophy trinucleotide repeat expansion on DMPK transcription and processing. Genomics. 28:1995;1-14.
66. Jansen G, Groenen PJTA, Bachner D, Jap PHK, Coerwinkel M, Oerlemans F, van der Broek W, Gohisch B, Pette D, Plomp JJ, et al. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat Genet. 13:1996;316-324.
67. Reddy S, Smith DBJ, Rich MM, Lererovich JM, Reilly P, Davis BM, Tran K, Rayburn H, Bronson R, Cros D, et al. Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet. 13:1996;325-335.
68. Caskey CT, Swanson MS, Timchenko LT. Myotonic dystrophy: discussion of molecular mechanism. Cold Spring Harbor Symp Quant Biol. 51:1996;607-614.
69. Timchenko LT, Timchenko NA, Caskey CT, Roberts R. Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy. Hum Mol Genet. 5:1996;115-121.
70. Timchenko LT, Miller JW, Timchenko NA, DeVore DR, Datar KV, Lin L, Roberts R, Caskey CT, Swanson MS. Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res. 24:1996;4407-4414.
71. Bhagwati S, Ghatpande A, Leung B. Identification of two nuclear proteins which bind to RNA CUG repeats: significance for myotonic dystrophy. Biochem Biophys Res Comm. 228:1996;55-62.
72. Boucher CA, King SK, Carey N, Krahe R, Winchester CL, Rahman S, Creavin T, Meghji P, Bailey MES, Chartier FL, et al. A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. Hum Mol Genet. 4:1995;1919-1925.
73. Klesert TR, Otten AD, Bird TD, Tapscott SJ. Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. of special interest Nat Genet. 16:1997;402-406 Demonstrated that the hypersensitive site between the DMPK and DMAHP genes can function as an enhancer, and that CTG expansions that eliminate the hypersensitive site also suppress expression of the DMAHP gene.
74. Heath SK, Carne S, Hoyle C, Johnson KJ, Wells DJ. Characterisation of expression of mDMAHP, a homeodomain-encoding gene at the murine DM locus. Hum Mol Genet. 6:1997;651-657.
75. Thornton CA, Wymer JP, Simmons Z, McClain C, Moxley RT III. Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. of special interest Nat Genet. 16:1997;407-409 DMAHP expression was shown to be reduced from the expanded allele in myoblasts, skeletal muscle, and myocardium. The degree of reduction correlated with the size of the expansion.
76. Otten AD, Tapscott SJ. Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci USA. 92:1995;5465-5469.
77. Kawakami K, Ohto H, Takizawa T, Saito T. Identification and expression of six family genes in mouse retina. FEBS Lett. 393:1996;259-263.
78. Kawakami K, Ohto H, Ikeda K, Roeder RG. Structure, function and expression of a murine homeobox protein AREC3, a homologue of Drosophila sine oculis gene product, and implication in development. Nucleic Acids Res. 24:1996;303-310.
79. Edstrom L, Wroblewski R. Intracellular elemental composition of single muscle fibers in muscular dystrophy and dystrophia myotonica. Acta Neurol Scand. 80:1989;419-424.
80. Gruener R, Stern LZ, Markovitz D, Gerdes C. Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases. Muscle Nerve. 2:1979;165-172.
81. Desnuelle C, Lombet A, Serratrice G, Lazdunski M. Sodium channel and sodium pump in normal and pathological muscles from patients with myotonic muscular dystrophy and lower motor neuron impairment. J Clin Invest. 69:1982;358-367.
82. Wevers RA, Joosten MG, van de Biezenbos JB, Theewes GM, Veerkamp JH. Excessive plasma K+ increase after ischemic exercise in myotonic muscular dystrophy. Muscle Nerve. 13:1990;27-32.
83. Benders AGM, Timmermans JAH, Oosterhof A, Ter Laak HJ, van Kuppevelt HMSM, Wevers RA, Veerkamp JH. Deficiency of Na+/K+-ATPase and sarcoplasmic reticulum Ca2+-ATPase in skeletal muscle and cultured muscle cells of myotonic dystrophy patients. Biochem J. 293:1993;269-274.
84. Takehana M. Hereditary cateract of the Nakano mouse. Exp Eye Res. 50:1990;671-676.
85. Harris S, Moncrieff C, Johnson K. Myotonic dystrophy: will the real gene please step forward. Hum Mol Genet. 5:1996;1417-1423.
86. Jansen G, Bachner D, Coerwinkel M, Wormskamp N, Hameister H, Wieringa B. Structural organization and developmental expression pattern of the WD-repeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus. Hum Mol Genet. 4:1995;843-852.
87. Shaw DJ, McCurrach M, Rundle SA, Harley HG, Crow SR, Sohn R, Thirion J-P, Hamshere MG, Buckler AJ, Harper PS, et al. Genomic organization and transcriptional units at the myotonic dystrophy locus. Genomics. 18:1993;673-679.
88. Shaw DJ, Chaudhary S, Rundle SA, Crow S, Brook JD, Harper PS, Harley HG. A study of DNA methylation in myotonic dystrophy. J Med Genet. 30:1993;189-192.
89. Jansen G, Bartolomei M, Kalscheuer V, Merkx G, Wormskamp N, Mariman E, Smeets D, Ropers HH, Wieringa B. No imprinting involved in the expression of DM-kinase mRNAs in mouse and human tissues. Hum Mol Genet. 2:1993;1221-1227.
90. Steinbach P, Glaser D, Vogel W, Wolf M, Schwemmle S. The DMPK gene of severely affected myotonic dystrophy patients is hypermethylated proximal to the largely expanded CTG repeat. of special interest Am J Hum Genet. 62:1998;278-285 Analysis using methylation sensitive restriction endonucleases demonstrated aberrant methylation in the region of the CTG repeat in cells from severe or congenital myotonic dystrophy. The aberrant methylation was associated with loss of in vivo footprinting at a consensus Sp 1 binding site.
91. Moxley RT III. Proximal myotonic myopathy: mini-review of a recently delineated clinical disorder. Neuromusc Dis. 6:1996;87-93.
92. Ricker K, Koch MC, Lehmann-Horn F, Pongratz D, Speich N, Reiners K, Schneider C, Moxley RT III. Proximal myotonic myopathy: Clinical features of a multisystem disorder similar to myotonic dystrophy. Arch Neurol. 52:1995;25-31.
93. Ricker K, Koch MC, Lehmann-Horn F, Pongratz D, Otto M, Heine R, Moxley RT III. Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. Neurology. 44:1994;1448-1452.
94. Abruzzese C, Krahe R, Liguori M, Tessarolo D, Siciliano MJ, Ashizawa T, Giacanelli M. Myotonic dystrophy phenotype without expansion of (CTG)n repeat: an entity distinct from proximal myotonic myopathy (PROMM)? J Neurol. 243:1996;715-721.
95. Wang Y-H, Amirhaeri S, Kang S, Wells RD, Griffith JD. Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene. Science. 265:1994;669-671.
96. Wang Y-H, Griffith J. Expanded CTG triplet blocks from the myotonic dystrophy gene create the strongest known natural nucleosome positioning elements. Genomics. 25:1995;570-573.
97. Godde JS, Wolffe AP. Nucleosome assembly on CTG triplet repeats. J Biol Chem. 271:1996;15222-15229.
98. Wang YH, Gellibollan R, Shimizu M, Wells RD, Griffith J. Long CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes. J Mol Biol. 263:1996;511-516.
99. Wang Y-H, Griffith JD. The [(G/C)3NN]n motif: a common DNA repeat that excludes nucleosomes. Proc Natl Acad Sci USA. 93:1996;8863-8867.
100. Wohrle D, Hennig I, Vogel W, Steinbach P. Mitotic sability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat Genet. 4:1993;140-142.
101. Drouin R, Angers M, Dallaire N, Rose TM, Khandjian W, Rousseau F. Structural and functional characterisation of the human FMR1 promoter reveals similarities with the hnkRNP-A2 promoter region. Hum Mol Genet. 6:1997;2051-2060.
102. Jalal SM, Lindor NM, Michels VV, Buckley DD, Hoppe DA, Sarkar G, Dewald GW. Absence of chromosome fragility at 19q13.3 in patients with myotonic dystrophy. Am J Med Genet. 46:1993;441-443.
103. Wenger SL, Giangreco CA, Tarleton J, Wessel HB. Inability to induce fragile sites at CTG repeats in congenital myotonic dystrophy. Am J Med Genet. 66:1996;60-63.
104. Freudenreich CH, Kantrow SM, Zakian VA. Expansion and length-dependent fragility of CTG repeats in yeast. Science. 279:1998;853-856.
105. 6AGG insertion within the CGG repeat of the FMR1 gene in Asians. Hum Genet. 99:1997;793-795.
106. Hirst MC, Arinami T, Laird CD. Sequence analysis of long FMR1 arrays from the Japanese population: insights into the generation of long (CGG)n tracts. Hum Genet. 101:1997;214-218.
107. Hirst M, Grewal P, Davies K. Precursor arrays for triplet repeat expansion at the fragile-X locus. Hum Mol Genet. 3:1994;1553-1560.