The neurology and corresponding genetics of fragile X disorders: Insights into the genetics of neurodegeneration

Future Neurology

Volumn 8, Issue 2, 2013, Pages 225-235

  Crum Bailey, Jennifer M ^a   Dennison, David H ^a   Weiner, William J ^b   Hawley, Jason S ^a  

^a WALTER REED ARMY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

ataxia; FMR1; fragile X syndrome; fragile X associated tremor ataxia syndrome; neurodegeneration; RNA toxicity; tremor

Indexed keywords

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

BRAIN RADIOGRAPHY; CLINICAL FEATURE; DEGENERATIVE DISEASE; DEVELOPMENTAL DISORDER; FMR1 GENE; FRAGILE X ASSOCIATED TREMOR ATAXIA SYNDROME; FRAGILE X SYNDROME; GENETIC COUNSELING; GENETICS; HISTOPATHOLOGY; HUMAN; NERVE DEGENERATION; NEUROLOGY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; TRINUCLEOTIDE REPEAT; X CHROMOSOME RECESSIVE DISORDER;

EID: 84874590820     PISSN: 14796708     EISSN: 17486971     Source Type: Journal    
DOI: 10.2217/fnl.12.92     Document Type: Review

References (66)

1. Turner G, Webb T, Wake S, Robinson H. Prevalence of fragile X syndrome. Am. J. Med. Genet. 64(1), 196-197 (1996).
2. Penrose LS. A Clinical and Genetic Study of 1280 Cases of Mental Defect. Her Majesty's Stationery Office. London, UK, Special Report Series, Medical Research Council, No. 229 (1938).
3. Martin JP, Bell J. A pedigree of mental defect showing sex-linkage. J. Neurol. Psychiatry 6(3-4), 154-157 (1943).
4. Lubs HA. A marker X chromosome. Am. J. Hum. Genet. 21(3), 231-244 (1969).
5. Harvey J, Judge C, Wiener S. Familial X-linked mental retardation with an X chromosome abnormality. J. Med. Genet. 14, 46-50 (1977).
6. Penagarikano O, Mulle JG, Warren ST. The pathophysiology of Fragile X Syndrome. Annu. Rev. Genomics Hum. Genet. 8, 109-129 (2007).
7. Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N. Trans-lational control of long-lasting synaptic plasticity and memory. Neuron 61, 10-26 (2009).
8. Pfeiffer BE, Huber KM. The state of synapses in fragile X syndrome. Neuroscientist 15(5), 549-567 (2009).
9. Darnell JC, Van Driesche SJ, Zhang C et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146(2), 247-261 (2011).
10. Hersh JH, Saul RA. Health supervision for children with fragile X syndrome. Pediatrics 127(5), 994-1006 (2011).
11. 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. 14(4), 249-270 (2005).
12. McConkie-Rosell A, Lachiewicz AM, Spiridigliozzi GA et al. Evidence that methylation of the FMR-I locus is responsible for variable phenotypic expression of the fragile X syndrome. Am. J. Hum. Genet. 53(4), 800-809 (1993).
13. Reiss AL, Hall SS. Fragile X syndrome: assessment and treatment implications. Child Adolesc. Psychiatr. Clin. N. Am. 16(3), 663-675 (2007).
14. Hagerman RJ, Berry-Kravis E, Kaufmann WE et al. Advances in the treatment of fragile X syndrome. Pediatrics 123(1), 378-390 (2009).
15. Visootsak J, Warren ST, Anido A, Graham JM. Fragile X syndrome: an update and review for the primary pediatrician. Clin. Pediatr. 44, 371-381 (2005).
16. Berry-Kravis E, Abrams L, Coffey SM et al. Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines. Mov. Disord. 22(14), 2018-2030, quiz 2140 (2007).
17. Brunberg JA, Jacquemont S, Hagerman RJ et al. Fragile X pre-mutation carriers: characteristic MR imaging findings in adult males with progressive cerebellar and cognitive dysfunction. Am. J. Neuroradiol. 23, 1757-1766 (2002).
18. Grigsby J, Bennett R, Brega A et al. Fragile X-associated tremor-ataxia syndrome (FXTAS): an X-linked neurodegenerative phenotype. Presented at: American College of Medical Genetics Meeting, Dallas, TX, USA, 17-20 March 2005 (Abstract 280).
19. Rodriguez-Revenga L, Madrigal I, Pagonabarraga J et al. Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur. J. Hum. Genet. 17, 1359-1362 (2009).
20. Hagerman RJ, Leehey M, Heinrichs W et al. Intention tremor, parkinsonism, and generalized brain atrophy in male carrriers of fragile X. Neurology 57, 127-130 (2001).
21. Jacquemont S, Hagerman RJ, Leehey M et al. Fraglie X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am. J. Hum. Genet. 72(4), 869-878 (2003).
22. Hall DA, O'Keefe JA. Fragile X-associated tremor ataxia syndrome: the expanding clinical picture, pathophysiology, epidemiology, and update on treatment. In: Tremor and Other Hyperkinetic Movements. Columbia University Academic Commons, NY, USA, 2 (2012).
23. Leehey MA, Berry-Kravis E, Min SJ et al. Progression of tremor and ataxia in male carriers of the FMR1 premutation. Mov. Disord. 22, 203-206 (2007).
24. Tassone F, Adams J, Berry-Kravis EM et al. CGG correlates with age of onset of motor signs of the fragile X-associated tremor/ ataxia syndrome (FXTAS). Am. J. Med. Genet. 144B(4), 566-569 (2012).
25. Peters N, Kamm C, Asmus F et al. Intrafamilia variability in fragile X-associated tremor/ataxia syndrome. Mov. Disord. 21, 98-102 (2006).
26. Grigsby J, Brega AG, Leehey MA et al. Impairment of executive cognitive functioning in males with fragile X-associated tremor/ ataxia syndrome. Mov. Disord. 22, 645-650 (2007).
27. Grigsby J, Leehey MA, Jacquemont S et al. Cognitive impairment in a 65-year-old male with the fragile X-associated tremor-ataxia syndrome (FXTAS). Cogn. Behav. Neurol. 19, 165-171 (2006).
28. Bak T, Crawford L, Hearn V, Mathuranath P, Hodges J. Subcortical dementia revisited: similarities and differences in cognitive function between progressive supranuclear palsy (PSP), cortico basal degeneration (CBD) and multiple system atrophy (MSA). Neurocase 11, 268-273 (2005).
29. Bacalman S, Farzin F, Bourgeois JA et al. Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia. J. Clin. Psych. 67, 87-94 (2006).
30. Bourgeois J, Cogswell J, Hessl D et al. Cognitive, anxiety, and mood disorders in the fragile X-associated tremor/ataxia syndrome (FXTAS). Gen. Hos. Psych. 29(4), 349-356 (2007).
31. Hagerman RJ, Hall DA, Coffey S et al. Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin. Interv. Aging 3, 251-262 (2008).
32. Louis E, Moskowitz C, Friez M, Amaya M, Vonsattel JP. Parkinsonism, dysautonomia, and intranuclear inclusions in a fragile X carrier: a clinical-pathological study. Mov. Disord. 21, 420-425 (2006).
33. Brunberg JA, Jacquemont S, Hagerman RJ et al. Fragile X pre-mutation carriers: characteristic MR imaging findings in adult males with progressive cerebellar and cognitive dysfunction. Am. J. Neuroradiol. 23, 1757-1766 (2002).
34. Greco CM, Berman RF. Martin RM et al. Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 129, 243-255 (2006).
35. Greco CM, Hagerman RJ, Tassone F et al. Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125, 1760-1771 (2002).
36. Tassone F, Hagerman RJ, Taylor AK et al. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile X-syndrome. Am. J. Hum. Genet. 66, 6-16 (2000).
37. Li Y, Jin P. RNA-mediated neurodegeneration in fragile X-associated tremor/ataxia syndrome. Brain Res. 1462, 112-117 (2006).
38. Cohen S, Masyn K, Adams J et al. Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome. Neurology 67, 1426-1431 (2006).
39. Wojciechowska M, Krzyzosiak WJ. CAG repeat RNA as an auxiliary toxic agent in polyglutamine disorders. RNA Biol. 8(4), 565-571 (2011).
40. Raske C, Hagerman PJ. Molecular pathogenesis of FXTAS. J. Investig. Med. 57(8), 825-829 (2009).
41. Yuan Y, Compton SA, Sobczak K et al. Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res. 35, 5474-5486 (2007).
42. Osborne RJ, Lin X, Welle S et al. Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy. Hum. Mol. Genet. 18(8), 1471-1481 (2009).
43. Jin P, Duan R, Qurashi A et al. Pur alpha binds to rCGG repeats and modulates repeatmediated neurodegeneration in a Drosphilia model of fragile X tremor/atanxia syndrome. Neuron 55, 556-564 (2007).
44. Tassone F, Adams J, Berry-Kravis EM et al. CGG repeat length correlates with age of onset of motor signs of the fragile X associated tremor ataxia syndrome (FXTAS). Am. J. Med. Gen. 144B, 566-569 (2007).
45. Napierala M, Michalowshi D, de Mezer M, Kryzososiak WJ. Facile FMR1 mRNA structure regulation by interruptions in CGG repeats. Nucleic Acids Res. 33, 451-463 (2005).
46. Mykowska A, Sobczak K, Wojciechowska M, Kozlowski P, Kryzosiak WM. CAG repeats mimic CUG repeats in the misregulation of alternative splicing. Nucleic Acids Res. 39(20), 8938-8951 (2011).
47. Iwahashi CK, Yasui DH, An HJ et al. Protein composition of the intranuclear inclusions of FXTAS. Brain 129, 256-271 (2006).
48. Sellier C, Rau F, Liu Y et al. Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J. 29, 1248-1261 (2010).
49. Sofola OA, Jin P, Qin Y et al. RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG permutation repeatinduced neurodegeneration in a Drosophila model of FXTAS. Neuron 55, 565-571 (2007).
50. Qurashi A, Li W, Zhou J-Y, Peng J, Jin P. Nuclear accumulation of stress response mRNAs contributes to the neurodegeneration caused by Fragile X premutation rCGG repeats. PLoS Genet. 7(6), e1002102 (2011).
51. Khalili K, Del Valle L, Muralidharan V et al. Pur alpha is essential for postnatal brain development and developmentally coupled cellular proliferation as revealed by genetic inactivation in the mouse. Mol. Cell. Biol. 23, 6857-6875 (2003).
52. Muslimov IA, Patel MV, Rose A et al. Spatial code recognition in neuronal RNA targeting: role of RNA-hnRNP A2 interactions. J. Cell. Biol. 194, 441-457 (2011).
53. Tan H, Poidevin M, Li H, Chen D, Jin P. MicroRNA-277 modulates the neurodegeneration caused by Fragile X premutation rCGG repeats. PLoS Genet. 8(5), e1002681 (2012).
54. Rodriguez-Revenga L, Madrigal I, Pagonabarraga J et al. Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur. J. Hum. Genet. 17, 1359-1362 (2009).
55. Nolin SL, Glicksman A, Ding X et al. Fragile X analysis of 1112 prenatal samples from 1991 to 2010. Prenat. Diagn. 31, 925-931 (2011).
56. Garcia-Arocena D, Hagerman PJ. Advances in understanding the molecular basis of FXTAS. Hum. Mol. Genet. 19, 83-89 (2010).
57. 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. 11(4), 306-310 (2009).
58. Hagerman RJ, Leavitt BR, Farzin F et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am. J. Hum. Genet. 74, 1051-1056 (2004).
59. Dombrowski C, Levesque ML, Morel ML, Rouillard P, Morgan K et al. Premutation and intermediate-size FMR1 alleles in 10 572 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. 11, 371-378 (2002).
60. Eichler EE, Kunst CB, Lugenbeel KA, Ryder OA, Davison D et al. Evolution of the cryptic FMR1 CGG repeat. Nat. Genet. 11, 301-308 (1995).
61. Ludwig AL, Raske C, Tassone F, Garcia-Arocena D, Hershey JW et al. Translation of the FMR1 mRNA is not influenced by AGG interruptions. Nucleic Acids Res. 37, 6896-6904 (2009).
62. Yrigollen CM, Tassone F, Durbin-Johnson B, Tassone F. The role of AGG interruptions in the transcription of FMR1 premutation alleles. PLoS ONE 6(7), e21728 (2011).
63. Hagerman PJ. Current gaps in understanding the molecular basis of FXTAS. Tremor Other Hyperkinet. Mov. (NY) 18(2), 63 (2012).
64. Wlodzimierz KJ, Sobszak K, Wojciechowska M, Fiszer A, Mykowska A, Kozlowski P. Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target. Nucleic Acids Res. 40, 11-26 (2012).
65. de Mezer M, Wojciechowska M, Napierala M, Sobczak K, Krzyzosiak WJ. Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference. Nuc. Acids Res. 39, 3852-3863 (2011). Website
66. Saul RA, Tarleton JC. FMR-1 related disorders. Gene Reviews™. Pagon RA, Bird TD, Dolan CR et al. (Eds). University of Washington, Seattle, WA, USA (2012). www.ncbi.nlm.nih.gov/books/NBK1384