Klinik Genetik Açıdan Frajil X Sendromu

Year 2018, Volume: 7 Issue: 4, 74 - 88, 28.12.2018

Elçin Latife Kurtoğlu Emine Demiral İbrahim Tekedereli

Abstract

Frajil X Sendromu, kalıtılabilir bilişsel geriliğin en sık sebebidir.
Tüm bilişsel gerilik nedenleri arasında da Down Sendromu’ndan sonra ikinci
sırada yer almaktadır. Etyolojisinde, X kromozomunda yer alan FMR1 geninin düzenleyici bölgesinde CGG
üçlü nükleotid tekrar sayısının artışı rol oynamaktadır. Bu tekrar artışı aynı
zamanda, sitogenetik çalışmalarla gösterilebilen, Xq27 bölgesinde kırılmalara
yol açmaktadır. Hastalık fenotipi, kuşaklar arasında ve cinsiyete göre
farklılık gösterebilmektedir. Tanısında farklı yöntemler kullanılmaktadır. Bu
çalışmada Frajil X sendromunun epidemiyolojisi, klinik özellikleri, tanı
yöntemleri ele alınmıştır.

Keywords

Frajil X Sendromu, Martin Bell Sendromu, Üçlü nükleotid tekrar artışı

References

• 1. Verkerk, A.J., Pieretti, M., Sutcliffe, J.S., Fu, Y.H., Kuhl, D.P., Pizzuti, A., et al. (1991). ‘‘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.
• 2. Saldarriaga, W., Tassone, F., Gonzalez-Teshima, L.Y., Forero-Forero, J.V., Ayala-Zapata, S., Hagerman, R. (2014). ‘‘Fragile X syndrome.’’ Colombia medica, 45:190-198.
• 3. Crawford, D.C., Acuna, J.M., Sherman, S.L. (2001). ‘‘ FMR1 and the fragile X syndrome: human genome epidemiology review.’’ Genetics in medicine, 3:359-371.
• 4. Mazzocco, M.M. (2000). ‘‘Advances in research on the fragile X syndrome.’’ Mental retardation and developmental disabilities research reviews, 6:96-106.
• 5. Coffee, B., Keith, K., Albizua, I., Malone, T., Mowrey, J., Sherman, S.L., et al. (2009). ‘‘Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA.’’ American journal of human genetics, 85:503-514.
• 6. Tuncbilek, E., Alikasifoglu, M., Boduroglu, K., Aktas, D., Anar, B. (1999). ‘‘Frequency of fragile X syndrome among Turkish patients with mental retardation of unknown etiology.’’ American journal of medical genetics, 84:202-203.
• 7. Demirhan, O., Tastemir, D., Diler, R.S., Firat, S., Avci, A. (2003). ‘‘A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.’’ Yonsei medical journal, 44:583-592.
• 8. Bilgen, T., Keser, I., Mihci, E., Haspolat, S., Tacoy, S., Luleci, G. (2005). ‘‘Molecular analysis of fragile X syndrome in Antalya Province.’’ Indian journal of medical sciences, 59:150-155.
• 9. Tabolacci, E., Chiurazzi, P. (2013). ‘‘Epigenetics, fragile X syndrome and transcriptional therapy.’’ American journal of medical genetics Part A, 161A:2797-2808.
• 10. Kim, M., Ceman, S. (2012). ‘‘Fragile X mental retardation protein: past, present and future.’’ Current protein & peptide science, 13:358-371.
• 11. Penagarikano, O., Mulle, J.G., Warren, S.T. (2007). ‘‘The pathophysiology of fragile x syndrome.’’ Annual review of genomics and human genetics, 8:109-129.
• 12. Beilina, A., Tassone, F., Schwartz, P.H., Sahota, P., Hagerman, P.J. (2004). ‘‘Redistribution of transcription start sites within the FMR1 promoter region with expansion of the downstream CGG-repeat element.’’ Human molecular genetics, 13:543-549.
• 13. Bagni, C., Oostra, B.A. (2013). ‘‘Fragile X syndrome: From protein function to therapy.’’ American journal of medical genetics Part A, 161A:2809-2821.
• 14. de Vries, B.B., Halley, D.J., Oostra, B.A., Niermeijer, M.F. (1998). ‘‘The fragile X syndrome.’’ Journal of medical genetics, 35:579-589.
• 15. Mila, M., Alvarez-Mora, M.I., Madrigal, I., Rodriguez-Revenga, L. (2017). ‘‘Fragile X syndrome: An overview and update of the FMR1 gene.’’ Clinical genetics, 93(2):197-205.
• 16. Gross, C., Hoffmann, A., Bassell, G.J., Berry-Kravis, E.M. (2015). ‘‘Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back.’’ Neurotherapeutics, 12:584-608.
• 17. Wijetunge, L.S., Chattarji, S., Wyllie, D.J., Kind, P.C. (2013). ‘‘Fragile X syndrome: from targets to treatments.’’ Neuropharmacology, 68:83-96.
• 18. De Boulle, K., Verkerk, A.J., Reyniers, E., Vits, L., Hendrickx, J., Van Roy, B., et al. (1993). ‘‘A point mutation in the FMR-1 gene associated with fragile X mental retardation.’’ Nature genetics, 3:31-35.
• 19. Tabolacci, E., Palumbo, F., Nobile, V., Neri, G. (2016). ‘‘Transcriptional Reactivation of the FMR1 Gene. A Possible Approach to the Treatment of the Fragile X Syndrome.’’ Genes (Basel), 7:E49.
• 20. Tabolacci, E., Neri, G. (2013). ‘‘Epigenetic modifications of the FMR1 gene.’’ Methods in molecular biology, 1010:141-153.
• 21. D'Hulst, C., Kooy, R.F. (2009). ‘‘Fragile X syndrome: from molecular genetics to therapy.’’ Journal of medical genetics, 46:577-584.
• 22. Cassidy, SB., McCandless, SE. (2005). ‘‘Management of Genetic Syndromes.’’ Management of Genetic Syndromes, C. SB and M. SE, eds. (Hoboken), pp 397-412.
• 23. Saul, R.A., Tarleton, J.C. (1993). ‘‘FMR1-Related Disorders. In GeneReviews((R)),’’ M.P. Adam, H.H. Ardinger, R.A. Pagon, S.E. Wallace, L.J.H. Bean, K. Stephens, et al., eds. (Seattle (WA).
• 24. Çarman, K.B. (2016). ‘‘Normal neuromotor development of children’’ Osmangazi Journal of Medicine, 38:17-19.
• 25. McConkie-Rosell, A., Finucane, B., Cronister, A., Abrams, L., Bennett, R.L., Pettersen, B.J. (2005). ‘‘Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors.’’ Journal of genetic counseling, 14:249-270.
• 26. Berry-Kravis, E. (2002). ‘‘Epilepsy in fragile X syndrome.’’ Developmental medicine and child neurology, 44:724-728.
• 27. Sherman, S.L. (2000). ‘‘Premature ovarian failure in the fragile X syndrome.’’ American journal of medical genetics, 97:189-194.
• 28. Hunter, J.E., Epstein, M.P., Tinker, S.W., Charen, K.H., Sherman, S.L. (2008). ‘‘Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.’’ Genetic epidemiology, 32:553-559.
• 29. Nelson, L.M., Covington, S.N., Rebar, R.W. (2005). ‘‘An update: spontaneous premature ovarian failure is not an early menopause.’’ Fertility and sterility, 83:1327-1332.
• 30. Tassone, F., Adams, J., Berry-Kravis, E.M., Cohen, S.S., Brusco, A., Leehey, M.A., et al. (2007). ‘‘CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS).’’ American journal of medical genetics Part B, 144B:566-569.
• 31. Cohen, S., Masyn, K., Adams, J., Hessl, D., Rivera, S., Tassone, F., et al. (2006). ‘‘Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome.’’ Neurology, 67:1426-1431.
• 32. Rodriguez-Revenga, L., Madrigal, I., Pagonabarraga, J., Xuncla, M., Badenas, C., Kulisevsky, J., et al. (2009). ‘‘Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families.’’ European journal of human genetics, 17:1359-1362.
• 33. Johnson, C.P., Myers, S.M., American Academy of Pediatrics Council on Children With, D. (2007). ‘‘Identification and evaluation of children with autism spectrum disorders.’’ Pediatrics, 120:1183-1215.
• 34. Biancalana, V., Glaeser, D., McQuaid, S., Steinbach, P. (2015). ‘‘EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders.’’ European journal of human genetics, 23:417-425.
• 35. Pastore, L.M., Johnson, J. (2014). ‘‘The FMR1 gene, infertility, and reproductive decision-making: a review.’’ Frontiers in genetics, 5:195.
• 36. Tassone, F. (2015). ‘‘Advanced technologies for the molecular diagnosis of fragile X syndrome ’’ Expert review of molecular diagnostics, 15:1465-1473.
• 37. Ciaccio, C., Fontana, L., Milani, D., Tabano, S., Miozzo, M., Esposito, S. (2017). ‘‘Fragile X syndrome: a review of clinical and molecular diagnoses.’’ Italian journal of pediatrics, 43:39.
• 38. Oostra, B.A., Willemsen, R. (2001). ‘‘Diagnostic tests for fragile X syndrome.’’ Expert review of molecular diagnostics, 1:226-232.
• 39. Sofocleous, C., Kolialexi, A., Mavrou, A. (2009). ‘‘Molecular diagnosis of Fragile X syndrome.’’ Expert review of molecular diagnostics, 9:23-30.
• 40. Pandey, U.B., Phadke, S.R., Mittal, B. (2004). ‘‘Molecular diagnosis and genetic counseling for fragile X mental retardation.’’ Neurology India, 52:36-42.
• 41. Rajan-Babu, I.S., Chong, S.S. (2016). ‘‘Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders.’’ Genes, 7:E87.
• 42. Hersh, J.H., Saul, R.A., Committee on, G. (2011). ‘‘Health supervision for children with fragile X syndrome.’’ Pediatrics, 127:994-1006.