Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Hagerman, R.J.; Hagerman, P.J. Fragile X Syndrome: Diagnosis, Treatment and Research, 3rd ed.; The John Hopkins University Press: Baltimore, MD, USA, 2002. [Google Scholar]
- Tejada, M.I. Síndrome X Frágil: Libro de Consulta Para Familias Y Profesionales, 1st ed.; Centro Español de Documentación sobre Discapacidad, del Real Patronato sobre Discapacidad: Madrid, Spain, 2006. [Google Scholar]
- Tejada, M.I.; Glover, G.; Martinez, F.; Guitart, M.; De Diego-Otero, Y.; Fernandez-Carvajal, I.; Ramos, F.J.; Hernandez-Chico, C.; Pintado, E.; Rosell, J.; et al. Molecular testing for fragile X: Analysis of 5062 tests from 1105 fragile X families—Performed in 12 clinical laboratories in spain. Biomed Res. Int. 2014, 2014, 195793. [Google Scholar] [CrossRef] [PubMed]
- Kremer, E.J.; Pritchard, M.; Lynch, M.; Yu, S.; Holman, K.; Baker, E.; Warren, S.T.; Schlessinger, D.; Sutherland, G.R.; Richards, R.I. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 1991, 252, 1711–1714. [Google Scholar] [CrossRef] [PubMed]
- Mila, M.; Ramos, F.; Tejada, M.I. Clinical guideline of gene FMR1-associated diseases: Fragile X syndrome, primary ovarian insufficiency and tremor-ataxia syndrome. Med. Clin. Barc. 2014, 142, 219–225. [Google Scholar] [PubMed]
- Tassone, F.; Hagerman, R.J.; Taylor, A.K.; Gane, L.W.; Godfrey, T.E.; Hagerman, P.J. Elevated levels of FMR1 mRNA in carrier males: A new mechanism of involvement in the fragile-X syndrome. Am. J. Hum. Genet. 2000, 66, 6–15. [Google Scholar] [CrossRef] [PubMed]
- Tejada, M.I.; Garcia-Alegria, E.; Bilbao, A.; Martinez-Bouzas, C.; Beristain, E.; Poch, M.; Ramos-Arroyo, M.A.; Lopez, B.; Fernandez Carvajal, I.; Ribate, M.P.; et al. Analysis of the molecular parameters that could predict the risk of manifesting premature ovarian failure in female premutation carriers of fragile X syndrome. Menopause 2008, 15, 945–949. [Google Scholar] [CrossRef] [PubMed]
- Hagerman, P.J.; Hagerman, R.J. Fragile X-associated tremor/ataxia syndrome. Ann. N. Y. Acad. Sci. 2015, 1338, 58–70. [Google Scholar] [CrossRef] [PubMed]
- Sherman, S.L.; Curnow, E.C.; Easley, C.A.; Jin, P.; Hukema, R.K.; Tejada, M.I.; Willemsen, R.; Usdin, K. Use of model systems to understand the etiology of fragile X-associated primary ovarian insufficiency (FXPOI). J. Neurodev. Disord. 2014, 6, 26. [Google Scholar] [CrossRef] [PubMed]
- Coffey, S.M.; Cook, K.; Tartaglia, N.; Tassone, F.; Nguyen, D.V.; Pan, R.; Bronsky, H.E.; Yuhas, J.; Borodyanskaya, M.; Grigsby, J.; et al. Expanded clinical phenotype of women with the FMR1 premutation. Am. J. Med. Genet. A 2008, 146A, 1009–1016. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez-Revenga, L.; Madrigal, I.; Pagonabarraga, J.; Xuncla, M.; Badenas, C.; Kulisevsky, J.; Gomez, B.; Mila, M. Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur. J. Hum. Genet. 2009, 17, 1359–1362. [Google Scholar] [CrossRef] [PubMed]
- Jacquemont, S.; Hagerman, R.J.; Leehey, M.A.; Hall, D.A.; Levine, R.A.; Brunberg, J.A.; Zhang, L.; Jardini, T.; Gane, L.W.; Harris, S.W.; et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2016, 291, 460–469. [Google Scholar] [CrossRef] [PubMed]
- Hall, D.A.; Birch, R.C.; Anheim, M.; Jonch, A.E.; Pintado, E.; O’Keefe, J.; Trollor, J.N.; Stebbins, G.T.; Hagerman, R.J.; Fahn, S.; et al. Emerging topics in FXTAS. J. Neurodev. Disord. 2014, 6, 31. [Google Scholar] [CrossRef] [PubMed]
- Hagerman, P. Fragile X-associated tremor/ataxia syndrome (FXTAS): Pathology and mechanisms. Acta Neuropathol. 2013, 126, 1–19. [Google Scholar] [CrossRef] [PubMed]
- Hagerman, R.; Hagerman, P. Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurol. 2013, 12, 786–798. [Google Scholar] [CrossRef]
- Brown, S.S.; Stanfield, A.C. Fragile X premutation carriers: A systematic review of neuroimaging findings. J. Neurol. Sci. 2015, 352, 19–28. [Google Scholar] [CrossRef] [PubMed]
- Adams, J.S.; Adams, P.E.; Nguyen, D.; Brunberg, J.A.; Tassone, F.; Zhang, W.; Koldewyn, K.; Rivera, S.M.; Grigsby, J.; Zhang, L.; et al. Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). Neurology 2007, 69, 851–859. [Google Scholar] [CrossRef] [PubMed]
- Brunberg, J.A.; Jacquemont, S.; Hagerman, R.J.; Berry-Kravis, E.M.; Grigsby, J.; Leehey, M.A.; Tassone, F.; Brown, W.T.; Greco, C.M.; Hagerman, P.J. Fragile X premutation carriers: Characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction. AJNR Am. J. Neuroradiol. 2002, 23, 1757–1766. [Google Scholar] [PubMed]
- Wheeler, A.C.; Bailey, D.B., Jr.; Berry-Kravis, E.; Greenberg, J.; Losh, M.; Mailick, M.; Mila, M.; Olichney, J.M.; Rodriguez-Revenga, L.; Sherman, S.; et al. Associated features in females with an FMR1 premutation. J. Neurodev. Disord. 2014, 6, 30. [Google Scholar] [CrossRef] [PubMed]
- Duran Dominguez, M.; Molina Carrillo, M.; Fernandez Toral, J.; Martinez Merino, T.; Lopez Aristegui, M.A.; Alvarez Retuerto, A.I.; Onaindia Urquijo, M.L.; Tejada Minguez, M.I. Molecular diagnosis of fragile X syndrome with polymerase chain reaction: Application of a diagnostic protocol in 50 families from northern spain. An. Esp. Pediatr. 2001, 54, 331–339. [Google Scholar] [PubMed]
- Braceras Izaguirre, L.; Markuerkiaga Zubigarai, M.; Elizondo López De Landache, I. Estimación de la Prevalencia de Hipotiroidismo en la Comunidad Autónoma del País Vasco a Partir del Consumo de Hormonas Tiroideas (2000–2006). In Farmacia de Atención Primaria: Publicación Periódica de Divulgación YExpresión Científica de la Sociedad Española de Farmacéuticos de Atención Primaria (SEFAP); 2007; Volume 5, pp. 49–54. ISSN 1698–4358. [Google Scholar]
- Cuadros, J.; Llaneza, P.; Mateu, S. Demografía y Epidemiología del Climaterio en España. In Libro Blanco de la Menopausia en España; Menopausia, EMISA: Madrid, Spain, 2000; pp. 15–23. [Google Scholar]
- Mendoza, N.; Julia, M.D.; Galliano, D.; Coronado, P.; Diaz, B.; Fontes, J.; Gallo, J.L.; Garcia, A.; Guinot, M.; Munnamy, M.; et al. Spanish consensus on premature menopause. Maturitas 2015, 80, 220–225. [Google Scholar] [CrossRef] [PubMed]
- Jacquemont, S.; Hagerman, R.J.; Leehey, M.; Grigsby, J.; Zhang, L.; Brunberg, J.A.; Greco, C.; Des Portes, V.; Jardini, T.; Levine, R.; et al. Fragile X premutation tremor/ataxia syndrome: Molecular, clinical, and neuroimaging correlates. Am. J. Hum. Genet. 2003, 72, 869–878. [Google Scholar] [CrossRef] [PubMed]
- Allen, E.G.; Grus, W.E.; Narayan, S.; Espinel, W.; Sherman, S.L. Approaches to identify genetic variants that influence the risk for onset of fragile X-associated primary ovarian insufficiency (FXPOI): A preliminary study. Front. Genet. 2014, 5, 260. [Google Scholar] [CrossRef] [PubMed]
- Sullivan, S.D.; Welt, C.; Sherman, S. FMR1 and the continuum of primary ovarian insufficiency. Semin. Reprod. Med. 2011, 29, 299–307. [Google Scholar] [CrossRef] [PubMed]
- García-Alegría, E.; Ibáñez, B.; Mínguez, M.; Poch, M.; Valiente, A.; Sanz-Parra, A.; Martinez-Bouzas, C.; Beristain, E.; Tejada, M.I. Analysis of FMR1gene expression in female premutation carriers using robust segmented linear regression models. RNA 2007, 13, 756–762. [Google Scholar] [CrossRef] [PubMed]
- Saldarriaga, W.; Lein, P.; Gonzalez Teshima, L.Y.; Isaza, C.; Rosa, L.; Polyak, A.; Hagerman, R.; Girirajan, S.; Silva, M.; Tassone, F. Phenobarbital use and neurological problems in FMR1 premutation carriers. Neurotoxicology 2016, 53, 141–147. [Google Scholar] [CrossRef] [PubMed]
- Osakidetza. Available online: www.osakidetza.euskadi.eus (accessed on 23 June 2016).
- Rodriguez-Revenga, L.; Madrigal, I.; Blanch-Rubio, J.; Elurbe, D.M.; Docampo, E.; Collado, A.; Vidal, J.; Carbonell, J.; Estivill, X.; Mila, M. Screening for the presence of FMR1 premutation alleles in women with fibromyalgia. Gene 2013, 512, 305–308. [Google Scholar] [CrossRef] [PubMed]
- Martorell, L.; Tondo, M.; Garcia-Fructuoso, F.; Naudo, M.; Alegre, C.; Gamez, J.; Genoves, J.; Poo, P. Screening for the presence of FMR1 premutation alleles in a Spanish population with fibromyalgia. Clin. Rheumatol 2012, 31, 1611–1615. [Google Scholar] [CrossRef] [PubMed]
- Reumatología Clínica. Available online: www.reumatologiaclinica.org (accessed on 23 June 2016).
Disorder | Sex | No. Individuals Reviewed | Affected Individuals | ||
---|---|---|---|---|---|
Total No. | % | Mean CGG Repeats of the PM Allele | |||
Thyroid dysfunction | Women | 147 | 22 | 14.96% | 84.91 ± 24.73 (range 55–180) |
Men | 41 | 1 | 2.43% | ||
Psychiatric disorders | Women | 147 | 41 | 27.89% | 80.33 ± 18.82 (range 55–137) |
Men | 41 | 8 | 19.15% | ||
Fibromyalgia | Women | 147 | 4 | 2.72% | 82.50 ± 16.94 (range 67–100) |
Men | 41 | 0 | 0% | ||
FXPOI | Women | 84 (>40 years) | 19 3 < 40 years old | 22.61% | 83.45 ± 14.41 (range 59–128) |
FXTAS | Women | 62 (>50 years) | 2 definite and 1 probable | 3.22% 1.61% | 87 ± 13.12 (range 67–101) |
Men | 21 (>50 years) | 6 definite and 1 probable | 28.57% 4.76% |
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Merino, S.; Ibarluzea, N.; Maortua, H.; Prieto, B.; Rouco, I.; López-Aríztegui, M.-A.; Tejada, M.-I. Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study. Genes 2016, 7, 90. https://doi.org/10.3390/genes7100090
Merino S, Ibarluzea N, Maortua H, Prieto B, Rouco I, López-Aríztegui M-A, Tejada M-I. Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study. Genes. 2016; 7(10):90. https://doi.org/10.3390/genes7100090
Chicago/Turabian StyleMerino, Sonia, Nekane Ibarluzea, Hiart Maortua, Begoña Prieto, Idoia Rouco, Maria-Asunción López-Aríztegui, and Maria-Isabel Tejada. 2016. "Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study" Genes 7, no. 10: 90. https://doi.org/10.3390/genes7100090
APA StyleMerino, S., Ibarluzea, N., Maortua, H., Prieto, B., Rouco, I., López-Aríztegui, M.-A., & Tejada, M.-I. (2016). Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study. Genes, 7(10), 90. https://doi.org/10.3390/genes7100090