Molecular diagnosis of Fragile X syndrome

Expert Review of Molecular Diagnostics

Volumn 9, Issue 1, 2009, Pages 23-30

  Sofocleous, Christalena ^a,b   Kolialexi, Aggeliki ^a   Mavrou, Ariadni ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b 'Ag Sophia' Children's Hospital   (Greece)

Author keywords

FMR1 gene; FMRP; Fragile X syndrome; Full mutation; ms PCR; Premutation; Southern blot analysis

Indexed keywords

ANTIBODY; FRAGILE X MENTAL RETARDATION PROTEIN;

FRAGILE X SYNDROME; GENE MUTATION; HUMAN; IMMUNOASSAY; IMMUNOCYTOCHEMISTRY; MENTAL DEFICIENCY; METHYLATION; POLYMERASE CHAIN REACTION; PRENATAL DIAGNOSIS; PROTEIN EXPRESSION; REVIEW; SCREENING; SCREENING TEST; SOUTHERN BLOTTING;

ANIMALS; BLOTTING, SOUTHERN; DNA METHYLATION; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; HUMANS; MOLECULAR DIAGNOSTIC TECHNIQUES; POLYMERASE CHAIN REACTION;

EID: 58149229035     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/14737159.9.1.23     Document Type: Review

References (78)

1. Crawford DC, Acuna JM, Sherman SL. FMR1 and the Fragile X syndrome: human genome epidemiology review. Genet. Med. 3, 359-371(2001).
2. Garber KB, Visootsak J, Warren ST. Fragile X syndrome. Eur. J. Hum. Genet. 16(6), 666-672 (2008). • Information on the clinical phenotype.
3. Jacky PB, Ahuja YR, Anyane-Yeboa K et al. Guidelines for the preparation and analysis of the Fragile X chromosome in lymphocytes. Am. J. Med. Genet. 38(2-3), 400-403 (1991).
4. Verkerk AJ, Pieretti M, Sutcliffe JS 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 65, 905-914 (1991). • First description of the FMR1 gene.
5. Yu S, Pritchard M, Kremer E et al. Fragile X genotype characterized by an unstable region of DNA. Science 24, 1179-1181 (1991).
6. Sutherland GR, Baker E. The common Fragile site in band q27 of the human X chromosome is not coincident with the Fragile-X. Clin. Genet. 37, 167 (1990).
7. Knight SJ, Flannery AV, Hirst MC et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental-retardation. Cell 74, 127-134 (1993).
8. Verheij C, Bakker CE, de Graaff E et al. Characterization and localization of the FMR-1 gene product associated with Fragile X syndrome. Nature 363(6431), 722-724 (1993). • First description of Fragile X mental retardation protein (FMRP).
9. Brown WT, Houck GE Jr, Jeziorowska A et al. Rapid Fragile X carrier screening and prenatal-diagnosis using a non-radioactive PCR test. JAMA 270, 1569-1575 (1993).
10. Fu YH, Kuhl DP, Pizzuti A et al. Variation of the CGG repeat at the Fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67, 1047-1058 (1991). • Description of the most common PCR reaction performed for the diagnosis of Fragile X syndrome (FXS).
11. Nolin SL, Glicksman A, Houck GE Jr, Brown WT, Dobkin CS. Mosaicism in Fragile X affected males. Am. J. Med. Genet. 51(4), 509-512 (1994).
12. Zhong N, Ju W, Pietrofesa J, Wang D, Dobkin C, Brown WT. Fragile X "gray zone" alleles: AGG patterns, expansion risks, and associated haplotypes. Am. J. Med. Genet. 64(2), 261-265 (1996).
13. 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, 249-270 (2005). • Provides useful information on genetic counseling.
14. Nolin SL, Brown TW, Glicksman A et al. Expansion of the Fragile X CGG repeat in females with premutation or intermediate alleles. Am. J. Hum. Genet. 72, 454-464 (2003).
15. Sofocleous C, Kitsiou S, Fryssira H et al. 10 years' experience in Fragile X testing among mentally retarded individuals in Greece: a molecular and epidemiological approach. In Vivo 22(4), 451-455 (2008). • Most recent large cohort study on the diagnosis of FXS.
16. Pieretti M, Zhang F, Fu YH et al. Absence of expression of the FMR1 gene in Fragile X syndrome. Cell 66, 817-822 (1991).
17. Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST. Mosaic FMR1 deletion causes Fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am. J. Med. Genet. A. 146A(10),1358-1367 (2008). • Information on other FXS causative mutations.
18. Bear MF, Huber KM, Warren ST. The mGluR theory of Fragile X mental retardation. Trends. Neurosci. 27, 370-377 (2004). •• Information on the role of FMRP.
19. Johnston C, Eliez S, Dyer-Friedman J et al. Neurobehavioral phenotype in carriers of the Fragile X premutation. Am. J. Med. Genet. 103, 314-319 (2001).
20. Wittenberger MD, Hagerman RJ, Sherman SL et al. The FMR1 premutation and reproduction. Fertil. Steril. 87, 456-465 (2007).
21. Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA. Fragile-X syndrome and Fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol. 6, 45-55 (2007).
22. Hagerman PJ, Hagerman RJ. The Fragile-X premutation: a maturing perspective. Am. J. Hum. Genet. 74(5), 805-816 (2004). • Valuable comments concerning the possible pathogenic impact of premutation.
23. Rousseau F, Heitz D, Biancalana V et al. Direct diagnosis by DNA analysis of the Fragile X syndrome of mental retardation. N. Engl. J. Med. 325, 1673-1681 (1991).
24. Rousseau F, Heitz D, Tarleton J et al. A multicenter study on genotype-phenotype correlations in the Fragile X syndrome, using direct diagnosis with probe StB 12.3: the first 2,253 cases. Am. J. Hum. Genet. 55, 225-237 (1994).
25. 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. 146A(1), 60-65. (2008).
26. Pergolizzi RG, Erster SH, Goonewardena P, Brown WT. Detection of full Fragile X mutation. Lancet 339, 271-272 (1992)
27. Houdayer C, Lemonnier A, Gerard M et al. Improved fluorescent PCR-based assay for sizing CGG repeats at the FRAXA locus. Clin. Chem. Lab. Med. 37, 397-402 (1999).
28. Saluto A, Brussino A, Tassone F 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. 7, 605-612 (2005).
29. Haddad LA, Mingroni-Netto RC, Vianna-Morgante AM, Pena SD. A PCR-based test suitable for screening for Fragile X syndrome among mentally retarded males. Hum. Genet. 97, 808-812 (1996).
30. Wang Q, Green E, Bobrow M, Mathew CG. A rapid, non-radioactive screening test for Fragile X mutations at the FRAXA and FRAXE loci. J. Med. Gene. 32, 170-173 (1995).
31. Tassone F, Pan R, Amiri K, Taylor AK, Hagerman JP. 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. 10, 43-49 (2008 ). •• Description of a novel PCR approach that may be used for population screening.
32. Clark SJ, Harrison J, Paul CL, Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 22, 2990-2997 (1994).
33. Panagopoulos I, Lassen C, Kristoffersson U, Aman P. A methylation PCR approach for detection of Fragile X syndrome. Hum. Mutat. 14, 71-79 (1999).
34. Zhou Y, Law HY, Boehm CD et al. Robust Fragile X (CGG)n genotype classification using a methylation specific triple PCR assay. J. Med. Genet. 41, 45 (2004).
35. Boyd VL, Moody KI, Karger AE, Livak KJ, Zon G, Burns JW. Methylation-dependent fragment separation: direct detection of DNA methylation by capillary electrophoresis of PCR products from bisulfite-converted genomic DNA. Anal. Biochem. 354, 266-273 (2006).
36. 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. 52, 1492-1500 (2006). •• Detailed descriptions of simple methylation specific PCR approaches.
37. Dahl C, Grønskov K, Larsen LA, Guldberg P, Brøndum-Nielsen K. A homogeneous assay for analysis of FMR1 promoter methylation in patients with Fragile X syndrome. Clin. Chem. 53, 790-793 (2007). •• Detailed descriptions of simple methylation specific PCR approaches.
38. Dahl C, Guldberg P. DNA methylation analysis techniques. Biogerontology 4, 233-250 (2003).
39. Dahl C, Guldberg P. A ligation assay for multiplex analysis of CpG methylation using bisulfite-treated DNA. Nucleic Acids Res. 35(21), e144 (2007). • Novel modifications of mass spectrometry-PCR approaches. They both represent procedures that may in the future be widely applied in FXS diagnosis.
40. Nygren AO, Lens SI, Carvalho R. Methylation-specific multiplex ligation-dependent probe amplification enables a rapid and reliable distinction between male FMR1 premutation and fullmutation alleles. J. Mol. Diagn. 10(6), 496-501 (2008). • Novel modifications of mass spectrometry-PCR approaches. They both represent procedures that may in the future be widely applied in FXS diagnosis.
41. Willemsen R, Mohkamsing S, de Vries B et al. Rapid antibody test for Fragile X syndrome. Lancet 345, 1147-1148 (1995).
42. De Vries BBA, Mohkamsing S, van den Ouweland AMW et al. Screening with the FMR1 protein test among mentally retarded males. Hum. Genet. 103, 520-522 (1998). •• Description of the FMRP test and proof of principle on the value of this test.
43. Willemsen R, Oosterwijk JC, Los FJ, Galjaard H, Oostra BA. Prenatal diagnosis of Fragile X syndrome. Lancet 348, 967-968 (1996).
44. Willemsen R, Los F, Mohkamsing S et al. Rapid antibody test for prenatal diagnosis of Fragile X syndrome on amniotic fluid cells: a new appraisal. J. Med. Genet. 3, 250-251 (1997).
45. Willemsen R , Anar B, De Diego Otero Y et al. Non-invasive test for Fragile X syndrome, using hair root analysis. Am. J. Hum. Genet. 65, 98-103 (1999). •• Description of the FMRP test and proof of principle on the value of this test.
46. Willemsen R, Bontekoe CJ, Severijnen LA, Oostra BA. Timing of the absence of FMR1 expression in full mutation chorionic villi. Hum. Genet. 110, 601-605 (2002).
47. Malcov M, Naiman T, Yosef DB et al. Preimplantation genetic diagnosis for Fragile X syndrome using multiplex nested PCR. Reprod. Biomed. Online 14(4), 515-521 (2007).
48. Wittenberger MD, Hagerman RJ, Sherman SL et al. The FMR1 premutation and reproduction. Fertil. Steril. 87(3), 456-465 (2007). • Description of an effective and reliable procedure for FXS preimplantation genetic diagnosis.
49. Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ. Elevated levels of FMR1 messenger RNA in carrier males: increased mRNA in Fragile X Males 235 new mechanism of involvement in the Fragile X syndrome. Am. J. Hum. Genet. 66, 6-15 (2000).
50. Kenneson A, Zhang F, Hagedorn CH, Warren ST. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and permutation carriers. Hum. Mol. Genet. 10, 1449-1454 (2001).
51. Mínguez M, Ibáñez B, Ribate MP et al. Risk of cognitive impairment in female premutation carriers of Fragile X premutation: analysis by means of robust segmented linear regression models. Am. J. Med. Genet. B. Neuropsychiatr. Genet. (2008) (Epub ahead of print). • Reports on the correlation between the number of CGG in the PM range and FMR1 mRNA levels.
52. Greco C, Hagerman RJ, Tassone F et al. Neuronal intranuclear inclusions in a new cerebellar tremor/ataxiasyndrome among Fragile X carriers. Brain 125, 1760-1771 (2002).
53. Hagerman PJ, Hagerman RJ. The Fragile-X premutation: a maturing perspective. Am. J. Hum. Genet. 74(5), 805-816 (2004).
54. Greco CM, Berman RF, Martin RM et al. Neuropathology of Fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 129(Pt 1), 243-255 (2006).
55. Brown V, Jin P, Ceman S et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in Fragile X syndrome. Cell 107(4), 477-487 (2001).
56. Bittel DC, Kibiryeva N, Butler MG. Whole genome microarray analysis of gene expression in subjects with Fragile X syndrome. Genet. Med. 9 (7), 464-472 (2007).
57. Larsen LA, Grønskov K, Nørgaard-Pedersen B, Brøndum-Nielsen K, Hasholt L, Vuust J. High-throughput analysis of Fragile X (CGG)n alleles in the normal and premutation range by PCR amplification and automated capillary electrophoresis. Hum. Genet. 100, 564-568 (1997).
58. Hecimovic S, Vlasic J, Barisic L, Markovic D, Culic V, Pavelic K. A simple and rapid analysis of triplet repeat diseases by expand long PCR. Clin. Chem. Lab. Med. 39, 1259-1262 (2001).
59. O'Connell CD, Atha DH, Jakupciak JP, Amos JA, Richie K. Standardization of PCR amplification for Fragile X trinucleotide repeat measurements. Clin. Genet. 61, 13-20 (2002).
60. Strom CM, Huang D, Li Y et al. Development of a novel, accurate, automated, rapid, high-throughput technique suitable for population-based carrier screening for Fragile X syndrome. Genet. Med. 9, 199-207 (2007). • Description of a novel technique suitable for population screening.
61. Pesso R, Berkenstadt M, Cuckle H et al. Screening for Fragile X syndrome in women of reproductive age. Prenat. Diagn. 20, 611-614 (2000).
62. Toledano-Alhadef H, Basel-Vanagaite L, Magal N et al. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am. J. Hum. Genet. 69, 351-360 (2001).
63. 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. 57, 1006-1018 (1995).
64. 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. 7, 212-216 (1999).
65. Ibarreta D, Elles R, Cassiman JJ, Rodriquez-Cerezo E, Dequeker E. Towards quality assurance and harmonization of genetic testing services in the European Union. Nat. Biotechnol. 22, 1230-1235 (2004). • Information on the necessity and the effect of genetic tests in general.
66. Knight SJ, Regan R, Nicod A et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 354(9191), 1676-1681 (1999).
67. Ahn JW, Mann K, Docherty Z, Mackie Ogilvie C. Submicroscopic chromosome imbalance in patients with developmental delay and/or dysmorphism referred specifically for Fragile X testing and karyotype analysis. Mol. Cytogenet. 1(1), 2 (2008).
68. Madrigal I, Rodríguez-Revenga L, Badenas C et al. MLPA as first screening method for the detection of microduplications and microdeletions in patients with X-linked mental retardation. Genet. Med. 9(2), 117-122 (2007).
69. Froyen G, Van Esch H, Bauters M et al. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum. Mutat. 28(10), 1034-1042 (2007). • Information on the value of a comparative genomic hybridization array in the elucidation of idiopathic mental retardation.
70. Falbo V, Floridia G, Tosto F et al. The Italian External Quality Assessment scheme for Fragile X syndrome: the results of a 5-year survey. Genet. Test. 12(2), 279-288 (2008). •• Important data concerning the need for quality assessment schemes to assure high-quality genetic testing.
71. Wilson AJ, Pratt MV, Phansalkar A et al. Consensus characterization of 16 FMR1 reference materials: a consortium study J. Mol. Diagn. 10(1), 2-12 (2008). •• Important data concerning the need for quality assessment schemes to assure high-quality genetic testing.
72. Irizarry RA, Ladd-Acosta C, Carvalho B et al. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome. Res. 18(5), 780-790 (2008).
73. Bardoni B, Davidovic L, Bensaid M, Khandjian EW. The Fragile X syndrome: exploring its molecular basis and seeking a treatment. Expert Rev. Mol. Med. 8(8), 1-16 (2006). • Data on the pathogenesis and the possible treatments of FXS as that is targeted guided by the roles proposed for FMRP.
74. The European Molecular Genetics Quality Network www.emqn.org/emqn/ BestPractice.html
75. Clinical Molecular Genetics Society http://cmgsweb.shared.hosting.zen.co. uk
76. National Fragile X Foundation www.nfxf.org
77. EuroGentest www.eurogentest.org
78. FRAXA - Fragile X Research Foundation www.fraxa.org