The fragile X mental retardation syndrome 20 years after the FMR1 gene discovery: An expanding universe of knowledge

Clinical Biochemist Reviews

Volumn 32, Issue 3, 2011, Pages 135-162

  Rousseau, François ^a,b,c,d   Labelle, Yves ^b,c,d   Bussières, Johanne ^c   Lindsay, Carmen ^c  

^a Réseau de Médecine Génétique Appliquée   (Canada)

^b CanGèneTest Research and Knowledge Network   (Canada)

^c LAVAL UNIVERSITY   (Canada)

^d UNIVERSITÉ LAVAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 82055196654     PISSN: 01598090     EISSN: 18380212     Source Type: Journal    
DOI: None     Document Type: Review

References (230)

1. Brosco JP, Mattingly M, Sanders LM. Impact of specific medical interventions on reducing the prevalence of mental retardation. Arch Pediatr Adolesc Med 2006;160:302-9.
2. Larson SA, Lakin KC, Anderson L, Kwak N, Lee JH, Anderson D. Prevalence of mental retardation and developmental disabilities: estimates from the 1994/1995 National Health Interview Survey Disability Supplements. Am J Ment Retard 2001;106:231-52.
3. Lehrke R. Theory of X-linkage of major intellectual traits. Am J Ment Defic 1972;76:611-9.
4. Fishburn J, Turner G, Daniel A, Brookwell R. The diagnosis and frequency of X-linked conditions in a cohort of moderately retarded males with affected brothers. Am J Med Genet 1983;14:713-24.
5. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 1991;66:817-22.
6. Oberle I, Rousseau F, Heitz D, Kretz C, Devys D, Hanauer A, et al. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 1991;252:1097-102.
7. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-14.
8. Bell MV, Hirst MC, Nakahori Y, MacKinnon RN, Roche A, Flint TJ, et al. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell 1991;64:861-6.
9. Vincent A, Heitz D, Petit C, Kretz C, Oberle I, Mandel JL. Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis. Nature 1991; 349:624-6.
10. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 1991;67:1047-58.
11. Rousseau F, Heitz D, Biancalana V, Blumenfeld S, Kretz C, Boué J, et al. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med 1991;325:1673-81.
12. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007;30:575-621.
13. Loesch DZ, Huggins RM, Hagerman RJ. Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev 2004;10:31-41.
14. Rousseau F, Heitz D, Tarleton J, MacPherson J, Malmgren H, Dahl N, et al. A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases. Am J Hum Genet 1994;55:225-37.
15. 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 1996;64:388-94.
16. Hagerman RJ. Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. J Dev Behav Pediatr 2006;27:63-74.
17. Rousseau F, Robb LJ, Rouillard P, Der Kaloustian VM. 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 1994;3:927-30.
18. de Vries BB, Wiegers AM, Smits AP, Mohkamsing S, Duivenvoorden HJ, Fryns JP, et al. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet 1996;58:1025-32.
19. Freund LS, Reiss AL, Abrams MT. Psychiatric disorders associated with fragile X in the young female. Pediatrics 1993;91:321-9.
20. Chudley AE, Hagerman RJ. Fragile X syndrome. J Pediatr 1987;110:821-31.
21. Lachiewicz AM, Dawson DV. Do young boys with fragile X syndrome have macroorchidism? Pediatrics 1994;93:992-5.
22. Beckel-Mitchener A, Greenough WT. Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome. Ment Retard Dev Disabil Res Rev 2004;10:53-9.
23. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 2001;98:161-7.
24. van Karnebeek CD, Jansweijer MC, Leenders AG, Offringa M, Hennekam RC. Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness. Eur J Hum Genet 2005;13:6-25.
25. Johnson VA. Checklist assessments of FMR1 gene mutation phenotypes. J Cult Divers 2008;15:117-31.
26. Guruju MR, Lavanya K, Thelma BK, Sujatha M, OmSai VR, Nagarathna V, et al. Assessment of a clinical checklist in the diagnosis of fragile X syndrome in India. J Clin Neurosci 2009;16:1305-10.
27. Harris SW, Hessl D, Goodlin-Jones B, Ferranti J, Bacalman S, Barbato I, et al. Autism profiles of males with fragile X syndrome. Am J Ment Retard 2008;113:427-38.
28. Kaufmann WE, Cortell R, Kau AS, Bukelis I, Tierney E, Gray RM, et al. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A 2004;129A: 225-34.
29. Rogers SJ, Wehner DE, Hagerman R. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001;22:409-17.
30. Brown WT, Jenkins EC, Cohen IL, Fisch GS, Wolf-Schein EG, Gross A, et al. Fragile X and autism: a multicenter survey. Am J Med Genet 1986;23:341-52.
31. Hagerman RJ, Jackson AW 3rd, Levitas A, Rimland B, Braden M. An analysis of autism in fifty males with the fragile X syndrome. Am J Med Genet 1986;23:359-74.
32. Belmonte MK, Bourgeron T. Fragile X syndrome and autism at the intersection of genetic and neural networks. Nat Neurosci 2006;9:1221-5.
33. Addington AM, Gauthier J, Piton A, Hamdan FF, Raymond A, Gogtay N, et al. A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders. Mol Psychiatry 2011;16:238-9.
34. Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, Moog U, et al. Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet 2010;42:489-91.
35. Noor A, Whibley A, Marshall CR, Gianakopoulos PJ, Piton A, Carson AR, et al. Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. Sci Transl Med 2010;2:49ra68.
36. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 2010;466:368-72.
37. Khandjian EW, Corbin F, Woerly S, Rousseau F. The fragile X mental retardation protein is associated with ribosomes. Nat Genet 1996;12:91-3.
38. Khandjian EW, Fortin A, Thibodeau A, Tremblay S, Côté F, Devys D, et al. A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture. Hum Mol Genet 1995;4:783-9.
39. Kumari D, Gabrielian A, Wheeler D, Usdin K. The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the Fragile X mental retardation gene promoter. Biochem J 2005;386: 297-303.
40. Smith KT, Nicholls RD, Reines D. The gene encoding the fragile X RNA-binding protein is controlled by nuclear respiratory factor 2 and the CREB family of transcription factors. Nucleic Acids Res 2006;34: 1205-15.
41. Coffee B, Zhang F, Warren ST, Reines D. Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nat Genet 1999;22:98-101.
42. Coffee B, Zhang F, Ceman S, Warren ST, Reines D. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am J Hum Genet 2002;71:923-32.
43. Kunkel TA. Nucleotide repeats. Slippery DNA and diseases. Nature 1993;365:207-8.
44. Richards RI, Sutherland GR. Simple repeat DNA is not replicated simply. Nat Genet 1994;6:114-6.
45. Pearson CE, Nichol Edamura K, Cleary JD. Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet 2005;6:729-42.
46. Ennis S, Murray A, Brightwell G, Morton NE, Jacobs PA. Closely linked cis-acting modifier of expansion of the CGG repeat in high risk FMR1 haplotypes. Hum Mutat 2007;28:1216-24.
47. Fisch GS, Snow K, Thibodeau SN, Chalifaux M, Holden JJ, Nelson DL, et al. The fragile X premutation in carriers and its effect on mutation size in offspring. Am J Hum Genet 1995;56:1147-55.
48. Moutou C, Vincent MC, Biancalana V, Mandel JL. Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic. Hum Mol Genet 1997;6:971-9.
49. Malter HE, Iber JC, Willemsen R, de Graaff E, Tarleton JC, Leisti J, et al. Characterization of the full fragile X syndrome mutation in fetal gametes. Nat Genet 1997;15:165-9.
50. Collins SC, Coffee B, Benke PJ, Berry-Kravis E, Gilbert F, Oostra B, et al. Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndromelike phenotype. PLoS One 2010;5:e9476.
51. Gedeon AK, Baker E, Robinson H, Partington MW, Gross B, Manca A, et al. Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat Genet 1992;1:341-4.
52. Hammond LS, Macias MM, Tarleton JC, Shashidhar Pai G. Fragile X syndrome and deletions in FMR1: new case and review of the literature. Am J Med Genet 1997;72:430-4.
53. Hirst M, Grewal P, Flannery A, Slatter R, Maher E, Barton D, et al. Two new cases of FMR1 deletion associated with mental impairment. Am J Hum Genet 1995;56:67-74.
54. Meijer H, de Graaff E, Merckx DM, Jongbloed RJ, de Die-Smulders CE, Engelen JJ, et al. 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 1994;3:615-20.
55. Tarleton J, Richie R, Schwartz C, Rao K, Aylsworth AS, Lachiewicz A. An extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype. Hum Mol Genet 1993;2:1973-4.
56. Wohrle D, Kotzot D, Hirst MC, Manca A, Korn B, Schmidt A, et al. A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. Am J Hum Genet 1992;51: 299-306.
57. De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 1993;3:31-5.
58. Lugenbeel KA, Peier AM, Carson NL, Chudley AE, Nelson DL. Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nat Genet 1995;10:483-5.
59. Collins SC, Bray SM, Suhl JA, Cutler DJ, Coffee B, Zwick ME, et al. Identification of novel FMR1 variants by massively parallel sequencing in developmentally delayed males. Am J Med Genet A 2010;152A:2512-20.
60. Chiurazzi P, Macpherson J, Sherman S, Neri G. Significance of linkage disequilibrium between the fragile X locus and its flanking markers. Am J Med Genet 1996;64:203-8.
61. Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K. Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. Am J Hum Genet 1995;57:1006-18.
62. Toledano-Alhadef H, Basel-Vanagaite L, Magal N, Davidov B, Ehrlich S, Drasinover V, et al. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 2001;69:351-60.
63. Oudet C, Mornet E, Serre JL, Thomas F, Lentes-Zengerling S, Kretz C, et al. Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes. Am J Hum Genet 1993;52:297-304.
64. Chakravarti A. Fragile X founder effect? Nat Genet 1992;1:237-8.
65. Morton NE, Macpherson JN. Population genetics of the fragile-X syndrome: multiallelic model for the FMR1 locus. Proc Natl Acad Sci USA 1992;89:4215-7.
66. Sullivan AK, Crawford DC, Scott EH, Leslie ML, Sherman SL. Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range. Am J Hum Genet 2002;70:1532-44.
67. Nolin SL, Brown WT, Glicksman A, Houck GE Jr, Gargano AD, Sullivan A, et al. Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet 2003;72:454-64.
68. Fernandez-Carvajal I, Lopez Posadas B, Pan R, Raske C, Hagerman PJ, Tassone F. Expansion of an FMR1 grey-zone allele to a full mutation in two generations. J Mol Diagn 2009;11:306-10.
69. Devys D, Lutz Y, Rouyer N, Bellocq JP, Mandel JL. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 1993;4:335-40.
70. Sittler A, Devys D, Weber C, Mandel JL. Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Hum Mol Genet 1996;5:95-102.
71. Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 1997;17:1539-47.
72. Hinds HL, Ashley CT, Sutcliffe JS, Nelson DL, Warren ST, Housman DE, et al. Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nat Genet 1993;3:36-43.
73. Zhang Y, O'Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, et al. The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. Embo J 1995;14:5358-66.
74. Bechara EG, Didiot MC, Melko M, Davidovic L, Bensaid M, Martin P, et al. A novel function for fragile X mental retardation protein in translational activation. PLoS Biol 2009;7:e16.
75. Davidovic L, Huot ME, Khandjian EW. Lost once, the Fragile X Mental Retardation protein is now back onto brain polyribosomes. RNA Biol 2005;2:1-3.
76. Davidovic L, Tremblay S, Gravel M, De Koninck P, Khandjian EW. [The fragile X syndrome: one protein missing and 1001 disoriented mRNAs]. Med Sci (Paris) 2006;22:41-6.
77. Khandjian EW, Huot ME, Tremblay S, Davidovic L, Mazroui R, Bardoni B. Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles. Proc Natl Acad Sci USA 2004;101:13357-62.
78. Corbin F, Bouillon M, Fortin A, Morin S, Rousseau F, Khandjian EW. The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes. Hum Mol Genet 1997;6:1465-72.
79. Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U. Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum Mol Genet 2001;10:329-38.
80. Li Z, Zhang Y, Ku L, Wilkinson KD, Warren ST, Feng Y. The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res 2001;29:2276-83.
81. Mazroui R, Huot ME, Tremblay S, Filion C, Labelle Y, Khandjian EW. Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum Mol Genet 2002;11:3007-17.
82. Brown V, Jin P, Ceman S, Darnell JC, O'Donnell WT, Tenenbaum SA, et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 2001;107:477-87.
83. Chen L, Yun SW, Seto J, Liu W, Toth M. The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences. Neuroscience 2003;120:1005-17.
84. Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 2001;107:489-99.
85. Schaeffer C, Bardoni B, Mandel JL, Ehresmann B, Ehresmann C, Moine H. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. Embo J 2001;20:4803-13.
86. Bechara E, Davidovic L, Melko M, Bensaid M, Tremblay S, Grosgeorge J, et al. Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure. Nucleic Acids Res 2007;35:299-306.
87. Darnell JC, Fraser CE, Mostovetsky O, Stefani G, Jones TA, Eddy SR, et al. Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev 2005;19:903-18.
88. Ceman S, O'Donnell WT, Reed M, Patton S, Pohl J, Warren ST. Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet 2003;12:3295-305.
89. Miyashiro KY, Beckel-Mitchener A, Purk TP, Becker KG, Barret T, Liu L, et al. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 2003;37:417-31.
90. Kao DI, Aldridge GM, Weiler IJ, Greenough WT. Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci USA 2010;107:15601-6.
91. Lu R, Wang H, Liang Z, Ku L, O'donnell WT, Li W, et al. The fragile X protein controls microtubuleassociated protein 1B translation and microtubule stability in brain neuron development. Proc Natl Acad Sci USA 2004;101:15201-6.
92. Yao A, Jin S, Li X, Liu Z, Ma X, Tang J, et al. Drosophila FMRP regulates microtubule network formation and axonal transport of mitochondria. Hum Mol Genet 2011;20:51-63.
93. The Dutch-Belgian Fragile X Consortium. Fmr1 knockout mice: a model to study fragile X mental retardation. Cell 1994;78:23-33.
94. Galvez R, Gopal AR, Greenough WT. Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome. Brain Res 2003;971:83-9.
95. Irwin SA, Idupulapati M, Gilbert ME, Harris JB, Chakravarti AB, Rogers EJ, et al. Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 2002;111:140-6.
96. Nimchinsky EA, Oberlander AM, Svoboda K. Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci 2001;21:5139-46.
97. Huber KM, Gallagher SM, Warren ST, Bear MF. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 2002;99:7746-50.
98. Suvrathan A, Hoeffer CA, Wong H, Klann E, Chattarji S. Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome. Proc Natl Acad Sci USA 2010;107:11591-6.
99. Zald DH. The human amygdala and the emotional evaluation of sensory stimuli. Brain Res Brain Res Rev 2003;41:88-123.
100. Gantois I, Bakker CE, Reyniers E, Willemsen R, D'Hooge R, De Deyn PP, et al. Restoring the phenotype of fragile X syndrome: insight from the mouse model. Curr Mol Med 2001;1:447-55.
101. Peier AM, McIlwain KL, Kenneson A, Warren ST, Paylor R, Nelson DL. (Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features. Hum Mol Genet 2000;9:1145-59.
102. Bontekoe CJ, Bakker CE, Nieuwenhuizen IM, van der Linde H, Lans H, de Lange D, et al. Instability of a (CGG)98 repeat in the Fmr1 promoter. Hum Mol Genet 2001;10:1693-9.
103. Brouwer JR, Mientjes EJ, Bakker CE, Nieuwenhuizen IM, Severijnen LA, Van der Linde HC, et al. Elevated Fmr1 mRNA levels and reduced protein expression in a mouse model with an unmethylated Fragile X full mutation. Exp Cell Res 2007;313:244-53.
104. Zhang YQ, Bailey AM, Matthies HJ, Renden RB, Smith MA, Speese SD, et al. Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 2001;107:591-603.
105. Zhang YQ, Broadie K. Fathoming fragile X in fruit flies. Trends Genet 2005;21:37-45.
106. Tucker B, Richards RI, Lardelli M. Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome. Hum Mol Genet 2006;15:3446-58.
107. Plasterk RH. Micro RNAs in animal development. Cell 2006;124:877-81.
108. Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 2006;29:77-103.
109. Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 2006;17:189-202.
110. Jin P, Alisch RS, Warren ST. RNA and microRNAs in fragile X mental retardation. Nat Cell Biol 2004;6: 1048-53.
111. Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J, Jongens TA, et al. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 2004;7:113-7.
112. Caudy AA, Myers M, Hannon GJ, Hammond SM. Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev 2002;16: 2491-6.
113. Ishizuka A, Siomi MC, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 2002;16:2497-508.
114. Lugli G, Larson J, Martone ME, Jones Y, Smalheiser NR. Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. J Neurochem 2005;94:896-905.
115. Xu XL, Li Y, Wang F, Gao FB. The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila. J Neurosci 2008;28:11883-9.
116. Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, et al. Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 2010;65:373-84.
117. Rousseau F, Heitz D, Biancalana V, Oberle I, Mandel JL. On some technical aspects of direct DNA diagnosis of the fragile X syndrome. Am J Med Genet 1992;43:197-207.
118. Strom CM, Crossley B, Redman JB, Buller A, Quan F, Peng M, et al. Molecular testing for Fragile X Syndrome: lessons learned from 119,232 tests performed in a clinical laboratory. Genet Med 2007;9:46-51.
119. Bailey DB Jr, Raspa M, Bishop E, Holiday D. No change in the age of diagnosis for fragile x syndrome: findings from a national parent survey. Pediatrics 2009;124: 527-33.
120. Berkenstadt M, Ries-Levavi L, Cuckle H, Peleg L, Barkai G. Preconceptional and prenatal screening for fragile X syndrome: experience with 40,000 tests. Prenat Diagn 2007;27:991-4.
121. Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85:503-14.
122. Lévesque S, Dombrowski C, Morel ML, Rehel R, Côté JS, Bussières J, et al. Screening and instability of FMR1 alleles in a prospective sample of 24,449 mothernewborn pairs from the general population. Clin Genet 2009;76:511-23.
123. Gecz J, Gedeon AK, Sutherland GR, Mulley JC. Identification of the gene FMR2, associated with FRAXE mental retardation. Nat Genet 1996;13:105-8.
124. Sofocleous C, Kolialexi A, Mavrou A. Molecular diagnosis of Fragile X syndrome. Expert Rev Mol Diagn 2009;9:23-30.
125. Nolin SL, Glicksman A, Houck GE Jr, Brown WT, Dobkin CS. Mosaicism in fragile X affected males. Am J Med Genet 1994;51:509-12.
126. Devys D, Biancalana V, Rousseau F, Boué J, Mandel JL, Oberlé I. Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development. Am J Med Genet 1992;43: 208-16.
127. Nolin SL, Ding XH, Houck GE, Brown WT, Dobkin C. Fragile X full mutation alleles composed of few alleles: implications for CGG repeat expansion. Am J Med Genet A 2008;146A:60-5.
128. Cohen IL, Nolin SL, Sudhalter V, Ding XH, Dobkin CS, Brown WT. Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males. Am J Med Genet 1996;64:365-9.
129. Hagerman RJ, Hull CE, Safanda JF, Carpenter I, Staley LW, O'Connor RA, et al. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet 1994;51:298-308.
130. Wöhrle D, Salat U, Gläser D, Mücke J, Meisel-Stosiek M, Schindler D, et al. Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats. J Med Genet 1998;35:103-11.
131. de Vries BB, Severijnen LA, Jacobs A, Olmer R, Halley DJ, Oostra BA, et al. FMRP expression studies in blood and hair roots in a fragile X family with methylation mosaics. J Med Genet 2003;40:535-9.
132. Luo XF, Zhong JM, Zhang XZ, Zou Y, Chen Y, Wu HP, et al. [Hair root fragile X mental retardation protein assay for the diagnosis of fragile X syndrome]. Zhongguo Dang Dai Er Ke Za Zhi 2009;11:817-20.
133. Potter NT. You can build it... but will they come?: the potential "expansion" of testing methodologies for fragile X syndrome. J Mol Diagn 2009;11:279-80.
134. Romero-Espinoza P, Rosales-Reynoso MA, Willemsen R, Barros-Núñez P. FMR1 protein expression in blood smears for fragile X syndrome diagnosis in a Mexican population sample. Genet Test Mol Biomarkers 2010;14:511-4.
135. Iwahashi C, Tassone F, Hagerman RJ, Yasui D, Parrott G, Nguyen D, et al. A quantitative ELISA assay for the fragile x mental retardation 1 protein. J Mol Diagn 2009;11:281-9.
136. Filipovic-Sadic S, Sah S, Chen L, Krosting J, Sekinger E, Zhang W, et al. A novel FMR1 PCR method for the routine detection of low abundance expanded alleles and full mutations in fragile X syndrome. Clin Chem 2010;56:399-408.
137. Saluto A, Brussino A, Tassone F, Arduino C, Cagnoli C, Pappi P, et al. An enhanced polymerase chain reaction assay to detect pre- and full mutation alleles of the fragile X mental retardation 1 gene. J Mol Diagn 2005;7:605-12.
138. Dodds ED, Tassone F, Hagerman PJ, Lebrilla CB. Polymerase chain reaction, nuclease digestion, and mass spectrometry based assay for the trinucleotide repeat status of the fragile X mental retardation 1 gene. Anal Chem 2009;81:5533-40.
139. Strom CM, Huang D, Li Y, Hantash FM, Rooke J, Potts SJ, et al. Development of a novel, accurate, automated, rapid, high-throughput technique suitable for population-based carrier screening for Fragile X syndrome. Genet Med 2007;9:199-207.
140. Hantash FM, Goos DG, Tsao D, Quan F, Buller-Burckle A, Peng M, et al. Qualitative assessment of FMR1 (CGG)n triplet repeat status in normal, intermediate, premutation, full mutation, and mosaic carriers in both sexes: Implications for fragile X syndrome carrier and newborn screening. Genet Med 2010;12:162-73.
141. Lyon E, Laver T, Yu P, Jama M, Young K, Zoccoli M, et al. A simple, high-throughput assay for Fragile X expanded alleles using triple repeat primed PCR and capillary electrophoresis. J Mol Diagn 2010;12:505-11.
142. Tassone F, Pan R, Amiri K, Taylor AK, Hagerman PJ. A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations. J Mol Diagn 2008;10:43-9.
143. Dahl C, Gronskov K, Larsen LA, Guldberg P, Brondum-Nielsen K. A homogeneous assay for analysis of FMR1 promoter methylation in patients with fragile X syndrome. Clin Chem 2007;53:790-3.
144. Karunasagar A, Pandit L, Kumar S, Karunasagar I, Karunasagar I. Use of methylation sensitive polymerase chain reaction for detection of fragile X full mutation & carrier state in males. Indian J Med Res 2005;122:429-33.
145. Nygren AO, Lens SI, Carvalho R. Methylation-specific multiplex ligation-dependent probe amplification enables a rapid and reliable distinction between male FMR1 premutation and full-mutation alleles. J Mol Diagn 2008;10:496-501.
146. Tzeng CC, Liou CP, Li CF, Lai MC, Tsai LP, Cho WC, et al. Methyl-CpG-binding PCR of bloodspots for confirmation of fragile X syndrome in males. J Biomed Biotechnol 2009;2009:643692.
147. Zhou Y, Lum JM, Yeo GH, Kiing J, Tay SK, Chong SS. Simplified molecular diagnosis of fragile X syndrome by fluorescent methylation-specific PCR and GeneScan analysis. Clin Chem 2006;52:1492-500.
148. Godler DE, Tassone F, Loesch DZ, Taylor AK, Gehling F, Hagerman RJ, et al. Methylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio. Hum Mol Genet 2010;19:1618-32.
149. Burlet P, Frydman N, Gigarel N, Kerbrat V, Tachdjian G, Feyereisen E, et al. Multiple displacement amplification improves PGD for fragile X syndrome. Mol Hum Reprod 2006;12:647-52.
150. Malcov M, Naiman T, Yosef DB, Carmon A, Mey-Raz N, Amit A, et al. Preimplantation genetic diagnosis for fragile X syndrome using multiplex nested PCR. Reprod Biomed Online 2007;14:515-21.
151. Payne DA, Mamotte CD, Gancberg D, Pazzagli M, van Schaik RH, Schimmel H, et al. Nucleic acid reference materials (NARMs): definitions and issues. Clin Chem Lab Med 2010;48:1531-5.
152. Hawkins M, Boyle J, Wright KE, Elles R, Ramsden SC, O'Grady A, et al. Preparation and validation of the first WHO international genetic reference panel for Fragile X syndrome. Eur J Hum Genet 2011;19:10-7.
153. Amos Wilson J, Pratt VM, Phansalkar A, Muralidharan K, Highsmith WE Jr, Beck JC, et al. Consensus characterization of 16 FMR1 reference materials: a consortium study. J Mol Diagn 2008;10:2-12.
154. Franke P, Leboyer M, Gänsicke M, Weiffenbach O, Biancalana V, Cornillet-Lefebre P, et al. Genotypephenotype relationship in female carriers of the premutation and full mutation of FMR-1. Psychiatry Res 1998;80:113-27.
155. Loesch DZ, Huggins RM, Bui QM, Taylor AK, Hagerman RJ. Relationship of deficits of FMR1 gene specific protein with physical phenotype of fragile X males and females in pedigrees: a new perspective. Am J Med Genet A 2003;118A:127-34.
156. Loesch DZ, Huggins RM, Taylor AK. Application of robust pedigree analysis in studies of complex genotypephenotype relationships in fragile X syndrome. Am J Med Genet 2002;107:136-42.
157. Alanay Y, Unal F, Turanli G, Alikaşifoǧlu M, Alehan D, Akyol U, et al. A multidisciplinary approach to the management of individuals with fragile X syndrome. J Intellect Disabil Res 2007;51:151-61.
158. Schwartz CE, Dean J, Howard-Peebles PN, Bugge M, Mikkelsen M, Tommerup N, et al. Obstetrical and gynecological complications in fragile X carriers: a multicenter study. Am J Med Genet 1994;51:400-2.
159. Sherman SL. Premature ovarian failure in the fragile X syndrome. Am J Med Genet 2000;97:189-94.
160. Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJ, Yang KT, Lee C, et al. Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data. Am J Med Genet 1999;83:322-5.
161. Hagerman RJ, Leavitt BR, Farzin F, Jacquemont S, Greco CM, Brunberg JA, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004;74:1051-6.
162. Hagerman RJ, Leehey M, Heinrichs W, Tassone F, Wilson R, Hills J, et al. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 2001;57:127-30.
163. Leehey MA. Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment. J Investig Med 2009;57:830-6.
164. Capelli LP, Goncalves MR, Leite CC, Barbosa ER, Nitrini R, Vianna-Morgante AM. The fragile x-associated tremor and ataxia syndrome (FXTAS). Arq Neuropsiquiatr 2010;68:791-8.
165. Amiri K, Hagerman RJ, Hagerman PJ. Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 2008;65:19-25.
166. Deng H, Le W, Jankovic J. Premutation alleles associated with Parkinson disease and essential tremor. JAMA 2004;292:1685-6.
167. Loesch DZ, Khaniani MS, Slater HR, Rubio JP, Bui QM, Kotschet K, et al. Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism. Clin Genet 2009;76:471-6.
168. Cilia R, Kraff J, Canesi M, Pezzoli G, Goldwurm S, Amiri K, et al. Screening for the presence of FMR1 premutation alleles in women with parkinsonism. Arch Neurol 2009;66:244-9.
169. Kraff J, Tang HT, Cilia R, Canesi M, Pezzoli G, Goldwurm S, et al. Screen for excess FMR1 premutation alleles among males with parkinsonism. Arch Neurol 2007;64:1002-6.
170. Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009;123:378-90.
171. Rueda JR, Ballesteros J, Tejada MI. Systematic review of pharmacological treatments in fragile X syndrome. BMC Neurol 2009;9:53.
172. Bardoni B, Davidovic L, Bensaid M, Khandjian EW. The fragile X syndrome: exploring its molecular basis and seeking a treatment. Expert Rev Mol Med 2006;8: 1-16.
173. Dong WK, Greenough WT. Plasticity of nonneuronal brain tissue: roles in developmental disorders. Ment Retard Dev Disabil Res Rev 2004;10:85-90.
174. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med 2001;134:657-62.
175. Crawford DC, Meadows KL, Newman JL, Taft LF, Scott E, Leslie M, et al. Prevalence of the fragile X syndrome in African-Americans. Am J Med Genet 2002;110:226-33.
176. Mitchell RJ, Holden JJ, Zhang C, Curlis Y, Slater HR, Burgess T, et al. FMR1 alleles in Tasmania: a screening study of the special educational needs population. Clin Genet 2005;67:38-46.
177. Youings SA, Murray A, Dennis N, Ennis S, Lewis C, McKechnie N, et al. FRAXA and FRAXE: the results of a five year survey. J Med Genet 2000;37:415-21.
178. Biancalana V, Beldjord C, Taillandier A, Szpiro-Tapia S, Cusin V, Gerson F, et al. Five years of molecular diagnosis of Fragile X syndrome (1997-2001): a collaborative study reporting 95% of the activity in France. Am J Med Genet A 2004;129A:218-24.
179. Ryynanen M, Heinonen S, Makkonen M, Kajanoja E, Mannermaa A, Pertti K. Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet 1999;7:212-6.
180. Murray J, Cuckle H, Taylor G, Hewison J. Screening for fragile X syndrome. Health Technol Assess 1997;1:i-iv, 1-71.
181. Pembrey ME, Barnicoat AJ, Carmichael B, Bobrow M, Turner G. An assessment of screening strategies for fragile X syndrome in the UK. Health Technol Assess 2001;5:1-95.
182. Song FJ, Barton P, Sleightholme V, Yao GL, Fry-Smith A. Screening for fragile X syndrome: a literature review and modelling study. Health Technol Assess 2003;7: 1-106.
183. Kornman LH, Nisbet DL, Liebelt J. Pre-conception and antenatal screening for the fragile site on the X-chromosome. Cochrane Database Syst Rev 2002;1:CD001806.
184. Hill MK, Archibald AD, Cohen J, Metcalfe SA. A systematic review of population screening for fragile X syndrome. Genet Med 2010;12:396-410.
185. Musci TJ, Moyer K. Prenatal carrier testing for fragile X: counseling issues and challenges. Obstet Gynecol Clin North Am 2010;37:61-70.
186. Ashley CT, Sutcliffe JS, Kunst CB, Leiner HA, Eichler EE, Nelson DL, et al. Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nat Genet 1993;4: 244-51.
187. Eichler EE, Richards S, Gibbs RA, Nelson DL. Fine structure of the human FMR1 gene. Hum Mol Genet 1993;2:1147-53.
188. Verkerk AJ, de Graaff E, De Boulle K, Eichler EE, Konecki DS, Reyniers E, et al. Alternative splicing in the fragile X gene FMR1. Hum Mol Genet 1993;2:399-404.
189. Bardoni B, Castets M, Huot ME, Schenck A, Adinolfi S, Corbin F, et al. 82-FIP, a novel FMRP (fragile X mental retardation protein) interacting protein, shows a cell cycle-dependent intracellular localization. Hum Mol Genet 2003;12:1689-98.
190. Bardoni B, Schenck A, Mandel JL. A novel RNAbinding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein. Hum Mol Genet 1999;8:2557-66.
191. Ceman S, Brown V, Warren ST. Isolation of an FMRPassociated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex. Mol Cell Biol 1999;19:7925-32.
192. Ceman S, Nelson R, Warren ST. Identification of mouse YB1/p50 as a component of the FMRP-associated mRNP particle. Biochem Biophys Res Commun 2000;279:904-8.
193. Chen Y, Sittler A, Yu M, Bardoni B, Wu G. [Screening of proteins interact with FMR1 by yeast two-hybrid system]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1998;20:173-8.
194. Davidovic L, Bechara E, Gravel M, Jaglin XH, Tremblay S, Sik A, et al. The nuclear microspherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons. Hum Mol Genet 2006;15:1525-38.
195. Davidovic L, Jaglin XH, Lepagnol-Bestel AM, Tremblay S, Simonneau M, Bardoni B, et al. The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules. Hum Mol Genet 2007;16:3047-58.
196. Gagne JP, Bonicalzi ME, Gagne P, Ouellet ME, Hendzel MJ, Poirier GG. Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles. Biochem J 2005;392:499-509.
197. Linder B, Plöttner O, Kroiss M, Hartmann E, Laggerbauer B, Meister G, et al. Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP. Hum Mol Genet 2008;17:3236-46.
198. Menon RP, Gibson TJ, Pastore A. The C terminus of fragile X mental retardation protein interacts with the multi-domain Ran-binding protein in the microtubuleorganising centre. J Mol Biol 2004;343:43-53.
199. Ramos A, Hollingworth D, Adinolfi S, Castets M, Kelly G, Frenkiel TA, et al. The structure of the N-terminal domain of the fragile X mental retardation protein: a platform for protein-protein interaction. Structure 2006;14:21-31.
200. Schenck A, Bardoni B, Moro A, Bagni C, Mandel JL. A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P. Proc Natl Acad Sci USA 2001;98:8844-9.
201. Siomi MC, Zhang Y, Siomi H, Dreyfuss G. 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 1996;16:3825-32.
202. Tamanini F, Van Unen L, Bakker C, Sacchi N, Galjaard H, Oostra BA, et al. Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P. Biochem J 1999;343:517-23.
203. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 469: Carrier screening for fragile X syndrome. Obstet Gynecol 2010;116:1008-10.
204. Working Group of the Genetic Screening Subcommittee of the Clinical Practice Committee. American College of Medical Genetics. Fragile X syndrome: diagnostic and carrier testing. Am J Med Genet 1994;53:380-1.
205. American Academy of Pediatrics Committee on Genetics. Health supervision for children with fragile X syndrome. Pediatrics 1996;98:297-300.
206. Chitayat D, Wyatt PR, Wilson RD, Johnson JA, Audibert F, Allen V, et al. Fragile X testing in obstetrics and gynaecology in Canada. J Obstet Gynaecol Can 2008;30:837-46.
207. Curry CJ, Stevenson RE, Aughton D, Byrne J, Carey JC, Cassidy S, et al. Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Am J Med Genet 1997;72:468-77.
208. Kronquist KE, Sherman SL, Spector EB. Clinical significance of tri-nucleotide repeats in Fragile X testing: a clarification of American College of Medical Genetics guidelines. Genet Med 2008;10:845-7.
209. Maddalena A, Richards CS, McGinniss MJ, Brothman A, Desnick RJ, Grier RE, et al. Technical standards and guidelines for fragile X: the first of a series of diseasespecific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics. Quality Assurance Subcommittee of the Laboratory Practice Committee. Genet Med 2001;3:200-5.
210. McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ. Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors. J Genet Couns 2005;14:249-270.
211. McConkie-Rosell A, Robinson H, Wake S, Staley LW, Heller K, Cronister A. Dissemination of genetic risk information to relatives in the fragile X syndrome: guidelines for genetic counselors. Am J Med Genet 1995;59:426-30.
212. McIntosh N, Gane LW, McConkie-Rosell A, Bennett RL. Genetic Counseling for Fragile X Syndrome: Recommendations of the National Society of Genetic Counselors. J Genet Couns 2000;9:303-25.
213. Oostra BA, Jacky PB, Brown WT, Rousseau F. Guidelines for the diagnosis of fragile X syndrome. National Fragile X Foundation. J Med Genet 1993;30:410-3.
214. Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med 2005;7:584-7.
215. Patsalis PC, Sismani C, Hettinger JA, Holden JJ, Lawson JS, Chalifoux M, et al. Frequencies of "greyzone" and premutation-size FMR1 CGG-repeat alleles in patients with developmental disability in Cyprus and Canada. Am J Med Genet 1999;84:195-7.
216. Crawford DC, Acuna JM, Sherman SL. FMR1 and the fragile X syndrome: human genome epidemiology review. Genet Med 2001;3:359-71.
217. Cronister A, DiMaio M, Mahoney MJ, Donnenfeld AE, Hallam S. Fragile X syndrome carrier screening in the prenatal genetic counseling setting. Genet Med 2005;7:246-50.
218. Dombrowski C, Levesque S, Morel ML, Rouillard P, Morgan K, Rousseau F. Premutation and intermediatesize FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet 2002;11:371-8.
219. Fernandez-Carvajal I, Walichiewicz P, Xiaosen X, Pan R, Hagerman PJ, Tassone F. Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. J Mol Diagn 2009;11:324-9.
220. Geva E, Yaron Y, Shomrat R, Ben-Yehuda A, Zabari S, Peretz H, et al. The risk of fragile X premutation expansion is lower in carriers detected by general prenatal screening than in carriers from known fragile X families. Genet Test 2000;4:289-92.
221. Huang KF, Chen WY, Tsai YC, Lin CC, Chen SH, Tseng CY, et al. Pilot screening for fragile X carrier in pregnant women of southern Taiwan. J Chin Med Assoc 2003;66:204-9.
222. Jacquemont S, Leehey MA, Hagerman RJ, Beckett LA, Hagerman PJ. Size bias of fragile X premutation alleles in late-onset movement disorders. J Med Genet 2006;43:804-9.
223. Rifé M, Badenas C, Mallolas J, Jiménez L, Cervera R, Maya A, et al. Incidence of fragile X in 5,000 consecutive newborn males. Genet Test 2003;7:339-43.
224. Saul RA, Friez M, Eaves K, Stapleton GA, Collins JS, Schwartz CE, et al. Fragile X syndrome detection in newborns-pilot study. Genet Med 2008;10:714-9.
225. Tzeng CC, Tsai LP, Hwu WL, Lin SJ, Chao MC, Jong YJ, et al. Prevalence of the FMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548-FRAXAC1 haplotype. Am J Med Genet A 2005;133A:37-43.
226. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 338: Screening for fragile X syndrome. Obstet Gynecol 2006;107:1483-5.
227. Spector EB, Kronquist KK. American College of Medical Genetics - Standards and Guidelines for Clinical Genetics Laboratories. 2006 Edition. http://www.acmg.net/Pages/ACMG_Activities/stds-2002/fx.htm (Accessed 7 December 2010).
228. Biancalana V, Steinbach P, Stenhouse S. The European Molecular Genetics Quality Network Draft Best Practice Guidelines for Molecular Analysis in Fragile X Syndrome. http://www.emqn.org/emqn/digitalAssets/0/233_EMQN_guidelines_FRAX_2006.pdf (Accessed 7 December 2010).
229. Macpherson J, Sawyer H. Clinical Molecular Genetics Society - Practice guidelines for molecular diagnosis of Fragile X Syndrome. http://www.cmgs.org/BPGs/pdfs%20current%20bpgs/Fragile%20X.pdf (Accessed 7 December 2010).
230. Beckett L, Yu Q, Long AN. The numbers behind fragile X: prevalence and economic impact. The National Fragile X Foundation Quarterly 2005;21:18-21.