Abstract
Dynamic mutations are caused by amplification of a trinucleotide or other simple sequence repeat, which leads to disease and/or expression of a fragile site (Richards and Sutherland 1992). In contrast to the mendelian inheritance observed in most hereditary disorders caused by point mutations, deletions, insertions, or duplications, dynamic mutations show non-mendelian inheritance, as the amplified repeat expands or, more rarely, contracts when transmitted from one generation to the next. In the normal population, these simple sequence repeats are small, but polymorphic, having a different length. Repeats in the normal size range are stably transmitted from one generation to the next. However, a minority of individuals have larger repeats that are meiotically unstable and generally expand upon transmission from one generation to the next. If the dynamic mutation causes disease, this progressive amplification is reflected in increasing frequency and severity of the disease in successive generations. When the repeat is below a specific threshold size in an individual of the older generations of the family, the disease may not manifest itself at all. However, when the repeat exceeds a threshold size in the progeny, the disease symptoms become clear. This phenomenon of increased disease severity with successive generations, characteristic of dynamic mutations, is called anticipation.
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References
Abitbol M, Menini C, Delezoide A-L, Rhyner T, Vekemans M, Mallet J (1993) Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human foetal brain. Nat Genet 4:147–153
Abrams MT, Reiss AL (1995) The neurobiology of fragile X syndrome. Ment Retard Dev Dis Res Rev 1:269–275
Allingham-Hawkins DJ, Ray PN (1995) FRAXE expansion is not a common etiological factor among developmentally delayed males. Am J Hum Genet 56:72–76
Ashley CT, Sutcliffe JS, Kunst CB, Leiner HA, Eichler EE, Nelson DL, Warren ST (1993a) Human and murine FMR1: alternative splicing and translational initiation downstream of the CGG repeat. Nat Genet 4:244–251
Ashley CT, Wilkinson KD, Reines D, Warren ST (1993b) FMR-1 protein: conserved RNP family domains and selective RNA binding. Science 262:563–566
Bakker CE, Verheij C, Willemsen R, van der Helm R, Oerlemans F, Vermey M, Bygrave A, Hoog-eveen AT, Oostra BA, Reyniers E, De Boulle K, D’Hooge R, Cras P, van Velzen D, Nagels G, Martin J-J, De Deyn PP, Darby JK, Willems PJ (1994) Fmrl knockout mice: a model to study fragile X mental retardation. Cell 78:23–33
Bassett AS, Husted J (1997) Anticipation or ascertainment bias in schizophrenia? Penrose’s familial mental illness sample. Am J Hum Genet 60:630–637
Bennetto L, Pennington BF (1996) The neuropsychology of fragile X syndrome. In: Hagerman RJ, Cronister A (eds) Fragile X syndrome: diagnosis, treatment, and research. Johns Hopkins University Press, Baltimore, Massachusetts, pp 210–248
Berger R, Bloomfield CD, Sutherland GR (1985) Report of the committe on chromosome rearrangements in neoplasia and on fragile sites. 8th Int Worksh on human gene mapping. Cy-togenet Cell Genet 40:490–535
Biancalana V, Taine L, Bouix J-C, Finck S, Chauvin A, De Verneuil H, Knight SJL, Stoll C, Lacombe D, Mandel J-L (1996) Expansion and methylation status at FRAXE can be detected on EcoRI blots used for FRAXA diagnosis: analysis of four FRAXE families with mild mental retardation in males. Am J Hum Genet 59:847–854
Bogerd HP, Fridell RA, Madore S, Cullen BR (1995) Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell 82:485–494
Boldog F, Gemmill RM, West J, Robinson M, Robinson L, Li E, Roche J, Todd S, Waggoner B, Lundstrom R, Jacobson J, Mullokandov MR, Klinger H, Drabkin HA (1997) Chromosome 3p14 homozygous deletions and sequence analysis of FRA3B. Hum Mol Genet 6:193–203
Bontekoe CJM, de Graaff E, Nieuwenhuizen IM, Willemsen R, Oostra BA (1997) FMR1 premutation allele is stable in mice. Eur J Hum Genet 5:293–298
Boulikas T (1993) Nuclear localisation signals (NLS). Crit Rev Eukaryot Gene Expr 3:193–227
Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion J-P, Hudson T, Sohn R, Zemelman B, Snell RG, Rundle SA, Crow S, Davies J, Shelbourne P, Buxton J, Jones C, Juvonen V, Johnson K, Harper PS, Shaw DJ, Housman DE (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 68:799–808
Brown WT (1996) The FRAXE syndrome: is it time for routine screening?. Am J Hum Genet 58:903–905
Burd CG, Dreyfuss G (1994) Conserved functions and diversity of functions of RNA binding proteins. Science 615-621
Butler MG, Brunschwig LK, Miller LK, Hagerman RJ (1992) Standards for selected anthropometric measurements in males with the fragile X syndrome. Pediatrics 89:1059–1062
Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel J-L, Cocozza S, Koenig M, Pandolfo M (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427
Carboneil P, López I, Gabarrön J, Bernabé MJ, Lucas JM, Guitart M, Gabau E, Glover G (1996) FRAXE mutation analysis in three Spanish families. Am J Med Genet 64:434–440
Chaudhuri JP (1972) On the origin and nature of achromatic lesions. Chromosomes Today 3:147–151
Chudley AE, Hagerman RJ (1987) Fragile X syndrome. J Pediatr 110:821–831
Cianchetti C, Sannio-Fancello G, Fratta A-L, Manconi F, Orano A, Pischedda M-P, Pruna D, Spinicci G, Archidiacono N, Filippi G (1991) Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families. Am J Med Genet 40:234–243
Clarke JT, Wilson PJ, Morris CP, Hopwood JJ, Richards RI, Sutherland GR, Ray PN (1992) Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome. Am J Hum Genet 51:316–322
Cohen C, Parry DAD (1990) α-Helical coiled coils and bundles: how to design an α-helical protein. Proteins 7:1–15
Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, Greenough WT (1997a) Abnormal dendritic spines in fragile Xknockout mice: maturation and pruning deficits. Proc Natl Acad Sci USA 94:5401–5404
Comery TA, Irwin SA, Patel ME, Gilbert ME, Kooy RF, Willems PJ, Oostra BA, Greenough WT (1997b) Abnormal dendritic spine morphology in fragile X syndrome: a role for the fragile-X mental retardation protein in spine maturation and pruning. Proc Soc Neuro sci: 96.9
Coy JF, Sedlacek Z, Bächner D, Hameister H, Joos S, Lichter P, Delius H, Poustka A (1995) Highly conserved 3’ UTR and expression pattern of FXR1 points to a divergent gene regulation of FXR1 and FMR1. Hum Mol Genet 4:2209–2218
Cronister A, Schreiner R, Wittenberger M, Amiri K, Harris K, Hagerman RJ (1991) The heterozygous fragile X female: historical, physical, cognitive and cytogenetic features. Am J Med Genet 38:269–274
Dahl N, Hu LJ, Chery M, Fardeau M, Gilgenkrantz S, Nivelon-Chevallier A, Sidaner-Noisette I, Mugneret F, Gouyon JB, Gal A (1995) Myotubular myopathy in a girl with a deletion at Xq27-q28 and unbalanced X inactivation assigns the MTM1 gene to a 600-kb region. Am J Hum Genet 56:1108–1115
David G, Abbas N, Stevanin G, Dürr A, Yvert G, Cancel G, Weber C, Imbert G, Saudou F, Antoniou E, Drabkin H, Gemmill R, Giunti P, Benomar A, Wood N, Ruberg M, Agid Y, Mandel J-L, Brice A (1997) Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 17:65–70
De Boulle K, Verkerk AJMH, Reyniers E, Vits L, Hendrickx J, van Roy B, van den Bos F, de Graaff E, Oostra BA, Willems PJ (1993) A point mutation in the FMR1 gene associated with fragile X mental retardation. Nat Genet 3:31–35
Deelen W, Bakker C, Halley DJ, Oostra BA (1994) Conservation of CGG region in FMR1 gene in mammals. Am J Med Genet 51:513–516
de Graaff E, Rouillard P, Willems PJ, Smits APT, Rousseau F, Oostra BA (1995a) Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients. Hum Mol Genet 4:45–49
de Graaff E, Willemsen R, Zhong N, de Die-Smulders CEM, Brown WT, Freling G, Oostra B (1995b) Instability of the CGG repeat and expression of the FMR1 protein in a male fragile X patient with a lung tumor. Am J Hum Genet 57:609–618
de Graaff E, De Vries BBA, Willemsen R, van Hemel JO, Mohkamsing S, Oostra BA, van den Ouweland AMW (1996) The fragile X phenotype in a mosaic male with a deletion showing expression of the FMR1 protein in 28% of the cells. Am J Med Genet 64:302–308
Deissler H, Wilm M, Genc B, Schmitz B, Ternes T, Naumann F, Mann M, Doerfler W (1997) Rapid protein sequencing by tandem mass spectrometry and cDNA cloning of p20-CGGBP. J Biol Chem 272:16761–16768
de Vries BBA, Wiegers AM, Smits APT, Mohkamsing S, Duivenvoorden HJ, Fryns J-P, Curfs LMG, Halley DJJ, Oostra BA, van den Ouweland AMW, Niermijer MF (1996) Mental status of females with an FMR1 gene full mutation. Am J Hum Genet 58:1025–1032
de Vries LBA (1997) The fragile X syndrome. Clinical, genetic and large scale diagnostic studies among mentally retarded individuals. PhD Thesis, Erasmus University, Rotterdam
Devys D, Biancalana V, Rousseau F, Boué J, Mandel JL, Oberlé I (1992) Analysis of full fragile X mutations in foetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development. Am J Med Genet 43:208–216
Devys D, Lutz Y, Rouyer N, Bellocq J-P, Mandel J-L (1993) The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 4:335–340
D’Hooge R, Nagels G, Franck F, Bakker CE, Reyniers E, Storm K, Kooy RF, Oostra BA, Willems PJ, De Deyn PP (1997) Mildly impaired water maze performance in male Fmr1 knockout mice. Neuroscience 76:367–376
Eberhart DE, Warren ST (1996) Nuclease sensitivity of permeabilized cells confirms altered chro-matin formation at the fragile X locus. Somat Cell Mol Genet 22:435–441
Eberhart DE, Malter HE, Feng Y, Warren ST (1996) The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localisation and nuclear export signals. Hum Mol Genet 5:1083–1091
Eichler EE, Richards S, Gibbs RA, Nelson DL (1993) Fine structure of the human FMR1 gene. Hum Mol Genet 2:1147–1153
Eichler EE, Holden JJA, Popovich BW, Reiss AL, Snow K, Thibodeau SN, Richards CS, Ward PA, Nelson DL (1995a) Length of uninterrupted CGG repeats determines instability in the FMR1 gene. Nat Genet 8:88–94
Eichler EE, Kunst CB, Lugenbeel KA, Ryder OA, Davison D, Warren ST, Nelson DL (1995b) Evolution of the cryptic FMR1 CGG repeat. Nat Genet 11:301–307
Falik-Zaccai TC, Shachak E, Yalon M, Lis Z, Borochowitz Z, Macpherson JN, Nelson DL, Eichler EE (1997) Predisposition to the fragile X syndrome in Jews of Tunesian descent is due to the absence of AGG interruptions on a rare mediterranean haplotype. Am J Hum Genet 60:103–112
Feng Y, Zhang F, Lokey LK, Chastain JL, Lakkis L, Eberhart D, Warren ST (1995) Translational suppression by trinucleotide repeat expansion at FMR1. Science 268:731–734
Feng Y, Lakkis L, Devys D, Warren ST (1995a) Quantitative comparison of FMR1 gene expression in normal and premutation alleles. Am J Hum Genet 56:106–113
Feng Y, Gutekunst C-A, Eberhart DE, Yi H, Warren ST, Hersch SM (1997b) Fragile X mental retardation protein: nudeocytoplasmic shuttling and association with somatodendritic ribos-omes. J Neurosci 17:1539–1547
Fischer U, Huber J, Boelens WC, Mattaj IW, Lührmann R (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82:475–483
Fridell RA, Benson RE, Hua J, Bogerd HP, Cullen BR (1996) A nuclear role for the fragile X mental retardation protein. EMBO J 15:5408–5414
Fritz CC, Zapp ML, Green MR (1995) A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature 376:530–533
Fryns J-P (1986) The female and the fragile X: a study of 144 obligate female carriers. Am J Med Genet 23:157–169
Fu Y-H, Kuhl DPA, Pizutti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJMH, Holden JJA, Fen-wick RG, Warren ST, Oostra BA, Nelson DL, Caskey CT (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047–1058
Gecz J, Gedeon AK, Sutherland GR, Mulley JC (1996) Identification of the gene FMR2, associated with FRAXE mental retardation. Nat Genet 13:105–108
Gecz J, Oostra BA, Hockey A, Carbonell P, Turner G, Haan EA, Sutherland GR, Mulley JC (1997) FMR2 expression in families with FRAXE mental retardation. Hum Mol Genet 6:435–441
Gedeon AK, Baker E, Robinson H, Partington MW, Gross B, Manca A, Korn B, Poustka A, Yu S, Sutherland GR, Mulley JC (1992) Fragile X syndrome without CCG amplification has an FMR1 deletion. Nature Genet 1:341–344
Gedeon AK, Keinänen M, Adès LC, Kääriäinen H, Gécz J, Baker E, Sutherland GR, Mulley JC (1995) Overlapping submicroscopic deletions in Xq28 in two unrelated boys with developmental disorders: identification of a gene near FRAXE. Am J Hum Genet 56:907–914
Gericke GS (1995) A paradigmatic shift in the approach to neuropsychiatric gene linkage may require an anthropogenetic perspective. Med Hypotheses 45:517–522
Giraud F, Ayme S, Mattei JF, Mattei MG (1976) Constitutional chromosomal breakage. Hum Genet 34:125–136
Gispert S, Santos N, Damen R, Voit T, Schulz J, Klockgether T, Orozco G, Kreuz F, Weissenbach J, Auburger G (1995) Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity. Am J Hum Genet 56:183–187
Glover TW, Stein CK (1988) Chromosome breakage and recombination at fragile sites. Am J Hum Genet 43:265–273
Godde JS, Kass SU, Hirst MC, Wolffe AP (1996) Nucleosome assembly on methylated CGG triplet repeats in the fragile X mental retardation gene 1 promotor. J Biol Chem 271:24325–24328
Godfraind J-M, Reyniers E, De Boulle K, D’Hooge R, De Deyn PP, Bakker CE, Oostra BA, Kooy RF, Willems PJ (1996) Long-term potentiation in the hippocampus of fragile X knockout mice. Am J Med Genet 64:246–251
Görlich D, Mattaj IW (1996) Nucleocytoplasmic transport. Science 271:1513–1518
Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM, Canaani E (1992) The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell 71:701–708
Gu YH, Lugenbeel KA, Vockley JG, Grody WW, Nelson DL (1994) A de novo deletion in FMR1 in a patient with developmental delay. Hum Mol Genet 3:1705–1706.
Gu Y, Shen Y, Gibbs RA, Nelson DL (1996) Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island. Nat Genet 13:109–113
Hagerman RJ (1996) Physical and behavioral phenotype. In: Hagerman RJ, Cronister A (eds) Fragile X syndrome: diagnosis, treatment, and research. Johns Hopkins University Press, Baltimore, Massachusetts, pp 3–87
Hagerman RJ, Jackson K, Amiri K, Silverman AC, O’Connor R, Sobesky W (1992) Girls with fragile X syndrome: physical and neurocognitive status and outcome. Pediatrics 89:395–400
Hagerman RJ, Hull CE, Safanda JF, Carpenter I, Staley LW, O’Connor RA, Seydel C, Mazzocco MMM, Snow K, Thibodeau SN, Kuhl D, Nelson DL, Caskey CT, Taylor AK (1994) High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet 51:298–308
Hamel BCJ, Smits APT, de Graaff E, Smeets DFCM, Schoute F, Eussen BHJ, Knight SJL, Davies KE, Assman-Hulsmans CFCH, Oostra BA (1994) Segregation of FRAXE in a large family: clinical, psychometric, cytogenetic, and molecular data. Am J Hum Genet 55:923–931
Hansen RS, Canfield TK, Lamb MM, Gartier SM, Laird CD (1993) Association of fragile X syndrome with delayed replication of the FMR1 gene. Cell 73:1403–1409
Hansen RS, Canfield TK, Fjeld AD, Mumm S, Laird CD, Gartler SM (1997) A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication. Proc Natl Acad Sci USA 94:4587–4592
Harris S, Moncrieff C, Johnson K (1996) Myotonie dystrophy: will the real gene please step forward! Hum Mol Genet 5:1417–1423
Hart PS, Olson SM, Crandall K, Tarleton J (1995) Fragile X syndrome resulting from a 400 bp deletion within the FMR1 gene. Am J Hum Genet 57:A1395
Hergersberg M, Matsuo K, Gassmann M, Schaffner W, Lüscher B, Rülicke T, Aguzzi A (1995) Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice. Hum Mol Genet 4:359–366
Hewett DR, Handt O, Hobson L, Mangelsdorf M, Eyre H, Sutherland GR, Schuffenhauer S, Richards RI (1997) Positional cloning of the bromodeoxuridine-inducible fragile site on human chromosome 10q25.2. Am J Hum Genet 61:723
Hinds HL, Ashley CT, Sutcliffe JS, Nelson DL, Warren ST, Housman DE, Schalling M (1993) Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nat Genet 3:36–43
Hinton VJ, Brown WT, Wisniewski K, Rudelli RD (1991) Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet 41:289–294
Hirst M, Grewal P, Flannery A, Slatter R, Maher E, Barton D, Fryns JP, Davies K (1995) Two new cases of FMR1 deletion associated with mental impairment. Am J Hum Genet 56:67–74
Holden JJA, Julien-Inalsingh C, Chalifoux M, Wing M, Scott E, Fidler K, Swift I, Maidment B, Knight SJL, Davies KE, White BN (1996) Trinucleotide repeat expansion in the FRAXE locus is not common among institutionalized individuals with non-specific developmental disabilities. Am J Med Genet 64:420–423
Izakovic V (1984) Homozygosity for fragile site at 17p12 in a 28-year old healthy man. Hum Genet 68:340–341
Jacobsen P, Hauge M, Henningsen K, Hobolth N, Mikkelsen M, Philip J (1973) An (11;21) translocation in four generations with chromosome 11 abnormalities in the offspring. A clinical, cytogenetical, and gene marker study. Hum Hered 23:568–585
Jalal SM, Lindor NM, Michels VV, Buckley DD, Hoppe DA, Sarkar G, Dewald GW (1993) Absence of chromosome fragility at 19q13.3 in patients with myotonic dystrophy. Am J Med Genet 46:441–443
Jones C, Penny L, Mattina T, Yu S, Baker E, Voullaire L, Langdon WY, Sutherland GR, Richards RI, Tunnacliffe A (1995) Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2. Nature 376:145–149
Kähkönen M, Tengström C, Alitalo T, Matilainen R, Kaski M, Airaksinen E (1989) Population cy-togenetics of folate-sensitive fragile sites. II. Autosomal rare fragile sites. Hum Genet 82:3–8
Kambach C, Mattaj IW (1992) Intracellular distribution of the U1A protein depends on active transport and nuclear binding to U1 snRNA. J Cell Biol 118:11–21
Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Narumiya S, Kakizuka A (1994) CAG expansions in a novel gene from Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–227
Kemper MB, Hagerman RJ, Ahmad RS, Mariner R (1988a) Cognitive profiles and the spectrum of clinical manifestations in heterozygous fragile (X) females. Am J Med Genet 23:139–156
Kemper MB, Hagerman RJ, Altshul-Stark D (1988b) Cognitive profiles of boys with the fragile X syndrome. Am J Med Genet 30:191–200
Khandjian EW, Fortin A, Thibodeau A, Tremblay S, Côté F, Devys D, Mandel J-L, Rousseau F (1995) A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture. Hum Mol Genet 4:783–789
Khandjian EW, Corbin F, Woerly S, Rousseau F (1996) The fragile X mental retardation protein is associated with ribosomes. Nat Genet 12:91–93
Kiledjian M, Dreyfuss G (1992) Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. EMBO J 11:2655–2664
Knight SJL, Flannery AV, Hirst MC, Campbell L, Christodoulou Z, Phelps SR, Pointon J, Middle-ton-Price HR, Barnicoat A, Pembrey ME, Holland J, Oostra BA, Bobrow M, Davies KE (1993) Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 74:127–134
Knight SJL, Voelckel MA, Hirst MC, Flannery AV, Moncla A, Davies KE (1994) Triplet repeat expansion at the FRAXE locus and X-linked mild mental handicap. Am J Hum Genet 55:81–86
Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T, Saito M, Tomoda A, Miike T, Naito H, Ikuta F, Tsuji S (1994) Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet 6:9–13
Kooy RF, D’Hooge R, Reyniers E, Bakker CE, Nagels G, De Boulle K, Storm K, Clincke G, De Deyn PP, Oostra BA, Willems PJ (1996) Transgenic mouse model for the fragile X syndrome. Am J Med Genet 64:241–245
Kooy RF, Oostra BA, Willems PJ (1997) Molecular detection of dynamic mutations. In: Adolph KW (ed) Human genome methods. CRC Press, Boca Raton, Florida, pp 23–53
Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warren ST, Schlessinger D, Sutherland GR, Richards RI (1991) Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252:1711–1714
Kunst CB, Warren ST (1994) Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles. Cell 77:853–861
La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinar and bulbar muscular atrophy. Nature 352:77–79
Lavedan CN, Garrett L, Nussbaum RL (1997) Trinucleotide repeats (CGG)22TGG(CGG)43TGG(CGG)21 from the fragile X gene remain stable in transgenic mice. Hum Genet 100:407–414
LeBeau MM, Rowley JD (1984) Heritable fragile sites and cancer. Nature 308:607–608
Loesch DZ, Hay DA (1988) Clinical features and reproductive patterns in fragile X female heterozygotes. J Med Genet 25:407–414
Lubs HA (1969) A marker X chromosome. Am J Hum Genet 21:231–244
Lugenbeel KA, Peier AM, Carson NL, Chudley AE, Nelson DL (1995) Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nat Genet 10:483–485
MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA, James M, Groot N, MacFarlane H, Jenkins B, Anderson MA, Wexler NS, Gusella JF, Bates GP, Bax-endale S, Hummerich H, Kirby S, North M, Youngman S, Mott R, Zehetner G, Sedlacek Z, Poustka A, Frischauf A-M, Lehrach H, Buckler AJ, Church D, Doucette-Stam L, O’Donovan MC, Riba-Ramirez L, Shah M, Stanton VP, Strobel SA, Draths KM, Wales JL, Dervan P, Hous-man DE, Altherr M, Shiang R, Thompson L, Fiedler T, Wasmuth JJ, Tagle D, Valdes J, Elmer L, Allard M, Castilla L, Swaroop M, Blanchard K, Collins FS, Snell R, Holloway T, Gillespie K, Shaw D, Harper PS (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983
Maes B, Fryns J-P, Van Walleghem M, Van den Berghe H (1994) Cognitive functioning and information processing of adult mentally retarded men with fragile-X syndrome. Am J Med Genet 50:190–200
Malmgren H, Steén-Bondeson M-L, Gustavson K-H, Seémanova E, Holmgren G, Oberlé I, Mandel J-L, Pettersson U, Dahl N (1992) Methylation and mutation patterns in the fragile X syndrome. Am J Med Genet 43:268–278
Malter HE, Iber JC, Willemsen R, de Graaff E, Tarleton JC, Leisti J, Warren ST, Oostra BA (1997) Characterization of the full fragile X syndrome mutation in foetal gametes. Nat Genet 15:165–169
Martin JP, Bell J (1943) A pedigree of mental defect showing sex-linkage. J Neurol Psychol 6:154–157
Mazzocco MMM, Pennington B, Hagerman RJ (1993) The neurocognitive phenotype of female carriers of fragile X: additional evidence for specificity. J Dev Behav Pediatr 14:328–335
McConcie-Rosell A, Lachiewicz AA, Spiridigliozzi GA, Tarleton J, Schoenwald S, Phelan MC, Goonewardena P, Ding X, Brown WT (1993) Evidence that methylation of the FMR1 locus is responsible for variant phenotypic expression of the fragile X syndrome. Am J Hum Genet 53:800–809
McInnis MG, McMahon FJ, Chase GA, Simpson SG, Ross CA, De Paulo JR Jr (1993) Anticipation in bipolar affective disorder. Am J Hum Genet 53:385–390
Meijer H, De Graaff E, Merckx DML, Jongbloed RJE, De Die-Smulders CEM, Engelen JJM, Fryns JP, Curfs PMG, Oostra BA (1994) A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome. Hum Mol Genet 3:615–620.
Melberg A, Arnell H, Dahl N, Stâlberg E, Raininko R, Oldfors A, Bakall B, Lundberg PO, Holme E (1996) Anticipation of autosomal dominant progressive external ophthalmoplegia with hy-pogonadism. Muscle Nerve 19:1561–1569
Merenstein SA, Sobesky WE, Taylor AK, Riddle JE, Tran HX, Hagerman RJ (1996) Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet 64:388–394
Meyer BE, Malim MH (1994) The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm. Genes Dev 8:1538–1547
Mila M, Castellvi, Barcelo A, Sanchez A, Jimenez D, Mandel J-L, Estivill X (1995) Mutations in the CpG island of the FMR1 gene: are they responsible for fragile X syndrome?. Am J Hum Genet 57:A1273
Mila M, Castellvi-Bel S, Sanchez A, Lazaro C, Villa M, Estivill X (1996) Mosaicism for the fragile X syndrome full mutation and deletions within the CGG repeat of the FMR1 gene. J Med Genet 33:338–340
Moran TH, Reeves RH, Rogers D, Fisher E (1996) Ain’t misbehavin’-it’s genetic! Nat Genet 12:115–116
Mornet E, Bogyo A, Deluchat C, Simon-Boouy B, Mathieu M, Thepot F, Grisard M.-C, Leguern E, Boue J, Boue A (1993) Molecular analysis of a ring chromosome X in a family with fragile X syndrome. Hum Genet 92:373–378
Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60
Morton JE, Bundey S, Webb TP, MacDonald F, Rindl PM, Bullock S (1997) Fragile X syndrome is less common than previously estimated. J Med Genet 34:1–5
Moutou C, Vincent M-C, Biancalana V, Mandel J-L (1997) Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic. Hum Mol Genet 6:971–979
Mulley JC, Yu S, Loesch DZ, Hay DA, Donnelly A, Gedeon AK, Carbonell P, López I, Glover G, Gabarrón I, Yu PWL, Baker E, Haan EA, Hockey A, Knight SJL, Davies KE, Richards RI, Sutherland GR (1995) FRAXE and mental retardation. J Med Genet 32:162–169
Murgia A, Polli R, Vinanzi C, Salis M, Drigo P, Artifoni L, Zacchello F (1996) Amplification of the Xq28 FRAXE repeats: extreme phenotype variability?. Am J Med Genet 64:441–444
Murray A, Macpherson JN, Pound MC, Sharrock A, Youings SA, Dennis NR, McKechnie N, Line-han P, Morton NE, Jacobs PA (1997) The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission. Hum Mol Genet 6:173–184
Musco G, Stier G, Joseph C, Castiglione Morelli MA, Nilges M, Gibson TJ, Pastore A (1996) Three-dimensional structure and stability of the KH domain: molecular insights into the fragile X syndrome. Cell 85:237–245
Nancarrow JK, Kremer E, Holman K, Eyre H, Doggett NA, Le Paslier D, Callen DF, Sutherland GR, Richards RI (1994) Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis. Science 264:1938–1941
Nandabalan K, Price L, Roeder GS (1993) Mutations in U1 snRNA bypass the requirement for a cell type-specific RNA splicing factor. Cell 73:407–415
Nasir J, Floresco SB, O’Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR (1995) Targeted disruption of the Huntington’s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81:811–823
Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM, Huebner K (1996) The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84:587–597
Oostra BA, Willems PJ (1995) A fragile gene. BioEssays 17:941–947
Oostra BA, Willems PJ, Verkerk AJMH (1993a) Fragile X syndrome: a growing gene. In: Davies KE, Tilghman SM (eds) Genome maps and neurological disorders. Cold Spring Harbor Laboratory Press, New York, pp 45–75
Oostra BA, Jacky PB, Brown WT, Rousseau F (1993b) Guidelines for the diagnosis of fragile X syndrome. J Med Genet 30:410–413
Orr HT, Chung M-y, Banfi S, Kwiatkowski TJ Jr, Servadio A, Beaudet AL, McCall AE, Duvick LA, Ranum LPW, Zoghbi HY (1993) Expansion of an unstable trinucleotide CAG repeat in spinoc-erebellar ataxia type 1. Nat Genet 4:221–226
Panté N, Aebi U (1996) Toward the molecular dissection of protein import into nuclei. Curr Opin Cell Biol 8:397–406
Parrish JE, Oostra BA, Verkerk AJMH, Richards CS, Reynolds J, Spikes AS, Shaffer LG, Nelson DL (1994) Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE. Nat Genet 8:229–235
Payami H, Bernard S, Larsen K, Kaye J, Nutt J (1995) Genetic anticipation in Parkinson’s disease. Neurology 45:135–138
Penny LA, Dell’Aquila M, Jones MC, Bergoffen J, Cunniff C, Fryns J-P, Grace E, Graham Jr JM, Kousseff B, Mattina T, Syme J, Voullaire L, Zelante L, Zenger-Hain J, Jones OW, Evans GA (1995) Clinical and molecular characterization of patients with distal 11q deletions. Am J Hum Genet 56:676–683
Pieretti M, Zhang F, Fu Y-H, Warren ST, Oostra BA, Caskey CT, Nelson DL (1991) Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66:817–822
Pivnick EK, Velagaleti G VN, Wilroy RS, Smith ME, Rose SR, Tipton RE, Tharapel AT (1996) Jacob-sen syndrome: report of a patient with severe eye anomalies, growth hormone deficiency, and hypothyroidism associated with deletion 11(q23q25) and review of 52 cases. J Med Genet 33:772–778
Price DK, Zhang F, Ashley CT Jr, Warren ST (1996) The chicken FMR1 gene is highly conserved with a CCT 5’-untranslated repeat and encodes an RNA-binding protein. Genomics 31:3–12
Pulkkinen L, Mannermaa A, Kajanoja E, Ryynananen M, Saarikoski S (1995) Deletion in the FMR1 gene in a fragile-X-male. Am J Hum Genet 57:A1300
Pulst S-M, Nechiporuk A, Nechiporuk T, Gispert S, Chen X-N, Lopes-Cendes I, Pearlman S, Starkman S, Orozco-Diaz G, Lunkes A, De Jong P, Rouleau GA, Auburger G, Korenberg JR, Figueroa C, Sahba S (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinoc-erebellar ataxia type 2. Nat Genet 14:269–276
Purpura DP (1974) Dendritic spine “dysgenesis” and mental retardation. Science 186:1126–1128
Quan F, Zonana J, Gunter K, Peterson KL, Magenis RE, Popovich BW (1995) An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. Am J Hum Genet 56:1042–1051
Reeves RH, Irving NG, Moran TH, Wohn A, Kitt C, Sisodia SS, Schmidt C, Bronson RT, Davisson MT (1995) A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11:177–184
Reiss AL, Abrams MT, Greenlaw R, Freund L, Denckla MB (1995) Neurodevelopmental effects of the FMR1 full mutation in humans. Nat Med 1:159–167
Reyniers E, Vits L, De Boulle K, van Roy B, van Velzen D, de Graaff E, Verkerk AJMH, Jorens HZJ, Darby JK, Oostra B, Willems PJ (1993) The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Nat Genet 4:143–146
Reyniers E, Martin J-J, Cras P, Van Marck E, Handig I, Jorens HZJ, Oostra BA, Kooy RF, Willems PJ (1998) Post-mortem examination of two fragile brothers with a full FMR1 mutation. Am J Med Genet (in press)
Richards RI, Holman K, Yu S, Sutherland GR (1993) Fragile X syndrome unstable element, p(CCG)n, and other simple tandem repeat sequences are binding sites for specific nuclear proteins. Hum Mol Genet 2:1429–1435
Richards RI, Sutherland GR (1992) Dynamic mutations: a new class of mutations causing human disease. Cell 70:709–712
Rousseau F, Heitz D, Biancalana V, Blumenfeld S, Kretz C, Boue J, Tommerup N, Van Der Hagen C, De Lozier-Blanchet C, Croquette MF, Gilgenkranz S, Jalbert P, Voelckel MA, Oberlé I, Mandel JL (1991) Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med 325:1673–1681
Rousseau F, Heitz D, Tarleton J, MacPherson J, Malmgren H, Dahl N, Barnicoat A, Mathew C, Mornet E, Tejada I, Maddalena A, Spiegel R, Schinzel A, Marcos JAG, Schorderet DF, Schaap T, Maccioni L, Russo S, Jacobs PA, Schwartz C, Mandel JL (1994a) A multicenter study on geno-type-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases. Am J Hum Genet 55:225–237
Rousseau F, Robb LJ, Rouilard P, Derkaloustian VM (1994b) No mental retardation in a man with 40% abnormal methylation at the FMR-1 locus and transmission of sperm cell mutations as premutations. Hum Mol Genet 3:927–930
Sanberg PR, Johnson DA, Moran TH, Coyle JT (1984) Investigating locomotion abnormalities in animal-models of extrapyramidal disorders-a commentary. Physiol Psychol 12:48–50
Schinzel A, der Maur P, Moser H (1977) Partial deletion of long arm of chromosome 11 [del(11)(q23)]: Jacobsen syndrome. Two new cases and review of the clinical findings. J Med Genet 14:438–444
Schmidt M, Certoma A, Du Sart D, Kalitsis P, Leversha M, Fowler K, Sheffield L, Jack I, Danks DM (1990) Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome. Hum Genet 84:347–352
Schmidt C, Henkel B, Pöschl E, Zorbas H, Puschke WG, Gloe TR, Müller PK (1992) Complete cDNA sequence of chicken vigilin, a novel protein with amplified and evolutionary conserved domains. Eur J Biochem 206:625–634
Sherman SL, Morton NE, Jacobs PA, Turner G (1984) The marker (X) chromosome: a cytogenetic and genetic analysis. Ann Hum Genet 48:21–37
Sherman SL, Jacobs PA, Morton NE, Froster-Iskenius U, Howard-Peebles PN, Nielsen KB, Partington NW, Sutherland GR, Turner G, Watson M (1985) Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet 69:3289–3299
Sijbers J, Scheunders P, Verhoye M, Van der Linden A, Van Dyck D, Raman E (1997) Watershed-based segmentation of 3D MR data for volume quantization. Magn Reson Imaging 15:679–688
Simko A, Hornstein L, Soukup S, Bagamery N (1989) Fragile X syndrome: recognition in young children. Pediatrics 83:547–552
Siomi H, Dreyfuss G (1995) A nuclear localisation domain in the hnRNP A1 protein. J Cell Biol 118:551–560
Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G (1993) The protein product of the fragile X gene, FMR1, has characteristics of an RNA binding protein. Cell 74:291–298
Siomi H, Choi M, Siomi MC, Nussbaum RL, Dreyfuss G (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 77:33–39
Siomi MC, Siomi H, Sauer WH, Srinivasan S, Nussbaum RL, Dreyfuss G (1995) FXR1, an auto-somal homolog of the fragile X mental retardation gene. EMBO J 14:2401–2408
Siomi MC, Zhang Y, Siomi H, Dreyfuss G (1996) Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Mol Cell Biol 16:3825–3832
Sittler A, Deyvs D, Weber C, Mandel J-L (1996) Alternative splicing of exon 14 determines nuclear or cytoplasmatic localisation of Fmrl protein isoforms. Hum Mol Genet 5:95–102
Slegtenhorst-Eegdeman KE, de Rooij DG, Verhoef-Post M, Ruiz A, Uilenbroek TJ, van de Kant HJG, Bakker CE, Oostra BA, Grootegoed JA, Themmen APN (1998) Macro-orchidism in Fmr1 knockout mice is caused by increased Sertoli cell proliferation during normal testes development. Endocrinology 139:156–162
Smeets DFCM, Scheres JMJC, Hustinx TWJ (1985) Heritable fragility at 11q13 and 12q13. Clin Genet 28:145–150
Smeets HJM, Smits APT, Verheij CE, Theelen JPG, Willemsen R, van de Burgt I, Hoogeveen AT, Oosterwijk JC, Oostra BA (1995) Normal phenotype in two brothers with a full FMR1 mutation. Hum Mol Genet 4:2103–2108
Snow K, Tester DJ, Kruckeberg KE, Schaid DJ, Thibodeau SN (1994) Sequence analysis of the fragile Xtrinucleotide repeat: implications for the origin of the fragile X mutation. Hum Mol Genet 3:1543–1551
Sobesky WE, Pennington BF, Porter D, Hull CE, Hagerman RJ (1994) Emotional and neurocog-nitive deficits in fragile X. Am J Med Genet 51:378–385
Subramanian PS, Nelson DL, Chinault AC (1996) Large domains of apparent delayed replication timing associated with triplet expansion at FRAXA and FRAXE. Am J Hum Genet 59:407–416
Sutherland GR (1977) Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science 197:265–266
Sutherland GR (1991) Chromosomal fragile sites. Genet Anal Tech Appl 8:161–166
Sutherland GR, Baker E (1992) Characterisation of a new rare fragile site easily confused with the fragile X. Hum Mol Genet 1:111–113
Sutherland GR, Hecht F (1985) Fragile sites on human chromosomes. Oxford University Press, New York
Tamanini F, Meijer N, Verheij C, Willems PJ, Galjaard H, Oostra BA, Hoogeveen AT (1996) FMRP is associated to the ribosomes via RNA. Hum Mol Genet 5:809–813
Tamanini F, Willemsen R, van Unen L, Bontekoe C, Galjaard H, Oostra BA, Hoogeveen AT (1997) Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. Hum Mol Genet 6:1315–1322
Tarleton J, Richie R, Schwartz C, Rao K, Aylsworth AS, Lachiewicz A (1993) An extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype. Hum Mol Genet 2:1973–1974
Tharapel AT, Anderson KP, Simpson JL, Martens PR, Wilroy R Jr, Llerena J Jr, Schwartz CE (1993) Deletion (X)(q26.1->q28) in a proband and her mother: molecular characterization and phenotypic-karyotypic deductions. Am J Hum Genet 52:463–471
Theobald TM, Hay DA, Judge C (1987) Individual variation and specific cognitive deficits in the fra(X) syndrome. Am J Med Genet 28:1–11
Trottier Y, Imbert G, Poustka A. Fryns JP, Mandel JL (1994) Male with typical fragile X phenotype is deleted for part of the FMR1 gene and for about 100 kb of upstream region. Am J Med Genet 51:454–457.
Turecki G, Smith MdAC, Mari JJ (1995) Type I bipolar disorder associated with a fragile site on chromosome 1. Am J Med Genet 60:179–182
Turner G, Webb T, Wake S, Robinson H (1996) Prevalence of fragile X syndrome. Am J Med Genet 64:196–197
Verheij C, Bakker CE, de Graaff E, Keulemans J, Willemsen R, Verkerk AJMH, Galjaard H, Reuser AJJ, Hoogeveen AT, Oostra BA (1993) Characterization and localisation of the FMR-1 gene product associated with fragile X syndrome. Nature 363:722–724
Verheij C, de Graaff E, Bakker CE, Willemsen R, Willems PJ, Meijer N, Galjaard H, Reuser AJJ, Oostra BA, Hoogeveen AT (1995) Characterization of FMR1 proteins isolated from different tissues. Hum Mol Genet 4:895–901
Verkerk AJMH, Pieretti M, Sutcliffe JS, Fu Y-H, Kuhl DPA, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang F, Eussen BE, van Ommen G-JB, Blonden LAJ, Riggins GJ, Chastain JL, Kunst CB, Galjaard H, Caskey CT, Nelson DL, Oostra BA, Warren ST (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 65:905–914
Verkerk AJMH, de Graaff E, De Boulle K, Eichler EE, Konecki DS, Reyniers E, Manca A, Poustka A, Willems PJ, Nelson DL, Oostra BA (1993) Alternative splicing in the fragile X gene FMR1. Hum Mol Genet 2:399–404
Verma IC, Elango R (1994) Variable expression of clinical features of Martin Bell syndrome in younger patients. Indian Pediatr 31:433–438
Voullaire LE, Webb GC, Leversha MA (1987) Chromosome deletion at 11q23 in an abnormal child from a family with inherited fragility at 11q23. Hum Genet 76:202–204
Wang Y-H, Griffith J (1996a) Methylation of expanded CCG triplet repeat DNA from fragile X syndrome patients enhances nucleosome exclusion. J Biol Chem 271:22937–22940
Wang Y-H, Griffith JD (1996b) The [(G/C)3NN]n motif: a common DNA repeat that excludes nudeosomes. Proc Natl Acad Sci USA 93:8863–8867
Wang Y-H, Amirhaeri S, Kang S, Wells RD, Griffith JD (1994) Preferential nucleosome assembly at the DNA triplet repeats from the myotonic dystrophy gene. Science 265:669–671
Wang Y-H, Gellibolian R, Shimizu M, Wells RD, Griffith J (1996) Long CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes. J Mol Biol 263:511–516
Weiler IJ, Irwin SA, Klintsova AY, Spencer CM, Brazelton AD, Miyashiro K, Comery TA, Patel B, Eberwine J, Greenough WT (1997) Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci USA 94:5395–5400
Wells RD (1996) Molecular basis of genetic instability of triplet repeats. J Biol Chem 271:2875–2878
Wen W, Meinkoth JL, Tsien RY, Taylor SS (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell 82:463–473
Willems PJ (1994) Dynamic mutations hit double figures. Nat Genet 8:213–215
Willems PJ, van Roy B, De Boulle K, Vits L, Reyniers E, Beck O, Dumon JE, Verkerk AJMH, Oostra B (1992) Segregation of the fragile X mutation from an affected male to his normal daughter. Hum Mol Genet 1:511–515
Willems PJ, Reyniers E, Oostra BA (1995) An animal model for fragile X syndrome. Ment Retard Dev Dis Res Rev 1:298–302
Willemsen R, Mohkamsing S, De Vries B, Devys D, van den Ouweland A, Mandel JL, Galjaard H, Oostra B (1995) Rapid antibody test for fragile X syndrome. Lancet 345:1147–1148
Willemsen R, Bontekoe C, Tamanini F, Galjaard H, Hoogeveen A, Oostra BA (1996) Association of FMRP with ribosomal precursor particles in the nucleolus. Biochem Biophys Res Commun 225:27–33
Wöhrle D, Hennig I, Vogel W, Steinbach P (1993) Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat Genet 4:140–142
Wolff DJ, Conroy J, Zurcher V, Gustashaw K, Ko L, Van Dyke DL, Weiss L, Willard HF, Schwartz S (1995) Deletions of ∼12 Mb of Xq including FMR1 results in a severe phenotype in a male and variable phenotypes in females depending upon the X inactivation pattern. Am J Hum Genet 57:A734
Yano-Yanagisawa H, Li Y, Wang H, Kohwi Y (1995) Single-stranded DNA binding proteins isolated from mouse brain recognize specific trinucleotide repeat sequences in vitro. Nucleic Acids Res 23:2654–2660
Yu S, Mangelsdorf M, Hewett D, Hobson L, Baker E, Eyre HJ, Lapsys N, Le Paslier D, Doggett NA, Sutherland GR, Richards RI (1997) Human chromosomal fragile site FRA16B is an amplified AT-rich minisatellite repeat. Cell 88:367–374
Yunis JJ, Soreng AL (1984) Constitutive fragile sites and cancer. Science 226:1199–1204
Zhang Y, O’Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, Dreyfuss G (1995) The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J 14:5358–5366
Zhong N, Ju W, Curley D, Wang D, Pietrofesa J, Wu G, Shen Y, Pang C, Poon P, Liu X, Gou S, Kajanoja E, Ryynänen M, Dobkin C, Brown WT (1996) A survey of FRAXE allele sizes in three populations. Am J Med Genet 64:415–419
Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Chi Lee C (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the a1A-voltage-dependent calcium channel. Nat Genet 15:62–69
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Kooy, R.F., Oostra, B.A., Willems, P.J. (1998). The Fragile X Syndrome and Other Fragile Site Disorders. In: Oostra, B.A. (eds) Trinucleotide Diseases and Instability. Results and Problems in Cell Differentiation, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69680-3_1
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