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Screening for the presence of FMR1 premutation alleles in a Spanish population with fibromyalgia

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Abstract

Fragile X mental retardation 1 (FMR1) premutation carriers, who are at risk of having children with fragile X Syndrome, were initially considered as clinically unaffected. However, recent clinical and molecular studies have shifted this point of view. The incidence of premutation in the general population is substantial. Apart from the well-documented fragile X-associated tremor–ataxia and fragile X premature ovarian insufficiency, there is a broad constellation of symptoms including depression, anxiety, muscle pain, autoimmune and thyroid disease, chronic fatigue, and fibromyalgia that has been described, particularly in females with the premutation (55–200 repeats). Fibromyalgia (FM) is the most common cause of widespread pain and comprises a heterogeneous group of patients, affecting 2–3 % of the general population. We analyzed the FMR1 gene in a cohort of females diagnosed with fibromyalgia in order to assess the incidence of premutated alleles. CGG repeat size was determined in 353 females suffering from FM and results were compared with a control group. Four premutated carriers in the FM group were detected. The observed incidence is higher than that described for a normal female population (1/88 vs 1/250). The early detection of premutation carriers for the FMR1 gene among individuals diagnosed with fibromyalgia is important and would be helpful in correct genetic counseling of patients and their families, who may be at risk of having children with fragile X syndrome, the most common known cause of inherited intellectual disability and autism. Our data should be cautiously interpreted based on just this study; nevertheless, screening for the FMR1 gene in FM patients at least with presentations suggestive of FMR1 gene-related disease seems recommendable.

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References

  1. Verkerk AJ, Pieretti M, Sutcliffe JS et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting lenght variation in fragile X syndrome. Cell 65:905–914

    Article  PubMed  CAS  Google Scholar 

  2. Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K (1995) Prevalence of carriers of premutation-size alleles of the FMR1 gene – and implications for the population genetics of the fragile X syndrome. Am J Hum Genet 57(5):1006–1018

    PubMed  CAS  Google Scholar 

  3. Hagerman PJ (2008) The fragile X prevalence paradox. J Med Genet 45(8):498–499

    Article  PubMed  Google Scholar 

  4. Oostra BA, Willemsen R (2009) FMR1: a gene with three faces. Biochem Biophys Acta 1790:467–477

    Article  PubMed  CAS  Google Scholar 

  5. Goodrich-Hunsaker N, Wong L, McLennan Y, Srivastava S, Tassone F, Harvey D, Rivera S, Simon T (2011) Young adult female fragile X premutation carriers show age- and genetically-modulated cognitive impairments. Brain and Cognition 75:255–260

    Article  PubMed  Google Scholar 

  6. Coffey SM, Cook K, Tartaglia N et al (2008) Expanded clinical phenotype of women with the FMR1 premutation. Am J Med Genet 146:1009–1016

    Article  Google Scholar 

  7. Rodriguez-Revenga L, Madrigal I, Pagonabarraga J et al (2009) Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet 11:79–89

    Google Scholar 

  8. Leehey MA, Legg W, Tassone F, Hagerman R (2011) Fibromyalgia in fragil X mental retardation 1 gene premutation carriers. Rheumatology 50:2233–2236

    Article  PubMed  CAS  Google Scholar 

  9. Di Franco M, Iannuccelli MC, Valesini G (2010) Neuroendocrine immunology of fibromyalgia. Ann N Y Acad Sci 1193:84–90

    Article  PubMed  Google Scholar 

  10. Yunus MB (2008) Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin Arthritis Rheum 37(6):339–352

    Article  PubMed  Google Scholar 

  11. Wolfe F, Smythe HA, Yunus MB et al (1990) The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum 33:160–172

    Article  PubMed  CAS  Google Scholar 

  12. Maniatis T, Firtsch EF, Sambrook J (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nuc Acids Res 16:1215

    Article  Google Scholar 

  13. Fu YH, Kuhl DPA, Pizzuti A et al (1991) Variation of the CGG repeat X site results in genetic instability. Resolution of Sherman paradox. Cell 67:1047–1058

    Article  PubMed  CAS  Google Scholar 

  14. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW (1992) Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51:1229–1239

    PubMed  CAS  Google Scholar 

  15. Cilia R, Kraff J, Canesi M et al (2009) Screening for the presence of FMR1 premutation alleles in women with parkinsonism. Arch Neurol 66(2):244–249

    Article  PubMed  Google Scholar 

  16. Seritan AL, Schneider A, Olichney JM (2009) LeeheyMA, AkinsRS, Hagerman RJ. Conversion disorder in women with the FMR1 premutation. Am J Med Genet 149A:2501–2506

    Article  PubMed  CAS  Google Scholar 

  17. Lachiewsicz A, Dawson D, Spiridigliozzi G, Cuccaro M, Lachiewsicz M, McConkie-Rosell A (2010) Indicators of anxiety and depression in women with the fragile X premutation: assessment of a clinical sample. J Intelect Disabil Res 54:597–610

    Article  Google Scholar 

  18. Yunus MB (2007) Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum 36:339–356

    Article  PubMed  Google Scholar 

  19. Wood PB, Schweinhardt P, Jaeger E et al (2007) Fibromyalgia patients show an abnormal dopamine response to pain. Eur J of Neuros 25:3576–3582

    Article  Google Scholar 

  20. Berry-Kravis E, Lewin F, Wuu J, Leehey M, Hagerman R, Hagerman P, Goetz CG (2003) Tremor and ataxia in fragile X premutation carriers: blinded videotape study. Ann Neurol 53:616–623

    Article  PubMed  CAS  Google Scholar 

  21. Garcia-Arocena D, Yang JE, Brouwer JR, Tassone F, Iwahashi C, Berry-Kravis EM, Goetz CG, Sumis AM, Zhou L, Nguyen DV, Campos L, Howell E, Ludwig A, Greco C, Willemsen R, Hagerman RJ, Hagerman PJ (2010) Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet 19:299–312

    Article  PubMed  CAS  Google Scholar 

  22. Iwahashi CK, Yasui DH, An HJ, Greco CM, Tassone F, Nannen K, Babineau B, Lebrilla CB, Hagerman RJ, Hagerman PJ (2006) Protein composition of the intranuclear inclusions of FXTAS. Brain 129:256–271

    Article  PubMed  CAS  Google Scholar 

  23. Tondo M, Gamez J, Gutierrez-Rivas E, Medel-Jimenez R, Martorell L. Genoptype and phenotype study of 34 spanish patients diagnosed with oculopharingeal muscular dysptrophy. J. Neurol. 2012. Jan 10. PubMed 22231868.

  24. Dombrowski C, Levesque S, Morel ML, Rouillard P, Morgan K, Rousseau F (2002) Premutation and intermediate-size FMR1 alleles in 10572 males form 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

    Article  PubMed  CAS  Google Scholar 

  25. Auvinen S, Suominen T, Hannonen P, Bachinski LL, Krahe R (2008) B. Udd B. Myotonic dystrophy type 2 found in two of sixty-three persons diagnosed as having fibromyalgia. Arthritis Rheum 58:3627–3631

    Article  PubMed  Google Scholar 

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Acknowledgments

We are indebted to all the patients who participated in our research for making this study possible. Thank to Dr. Sylvie Guiroux, form the Center de Reserche en génétiquehumanine et moléculaire, CHUQ, Québec, Canada, for kindly supplying us the StB12.3 probe. We also want to thank Katherine Andrews for assisting in language support.

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Authors and Affiliations

  1. Molecular Genetics Section, Hospital Sant Joan de Deu, Edifici docent C/ Santa Rosa 39, 08950, Barcelona, Spain

    Loreto Martorell, Mireia Tondo, Montserrat Naudo & Jordi Genovés

  2. Rheumatology Department, CIMA Clinic, Barcelona, Spain

    Ferrán Garcia-Fructuoso

  3. Rehumatology Department, Hospital de la Vall d’Hebron and Institut Universitari Dexeus, Barcelona, Spain

    Cayetano Alegre

  4. Neurology Department, Hospital de la Vall d’Hebron, Barcelona, Spain

    Josep Gamez

  5. Neurology Department, Hospital Sant Joan de Deu, Barcelona, Spain

    Pilar Poo

Authors
  1. Loreto Martorell
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  2. Mireia Tondo
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  3. Ferrán Garcia-Fructuoso
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  4. Montserrat Naudo
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  5. Cayetano Alegre
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  6. Josep Gamez
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  7. Jordi Genovés
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Correspondence to Loreto Martorell.

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Martorell, L., Tondo, M., Garcia-Fructuoso, F. et al. Screening for the presence of FMR1 premutation alleles in a Spanish population with fibromyalgia. Clin Rheumatol 31, 1611–1615 (2012). https://doi.org/10.1007/s10067-012-2052-y

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  • DOI: https://doi.org/10.1007/s10067-012-2052-y

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