{"id":8870,"date":"2020-12-10T12:02:43","date_gmt":"2020-12-10T09:02:43","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=8870"},"modified":"2020-12-10T12:04:36","modified_gmt":"2020-12-10T09:04:36","slug":"fragile-x-sendromu","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/fragile-x-sendromu\/","title":{"rendered":"FRAGILE X SENDROMU"},"content":{"rendered":"\n

Fragile X Sendromu, X kromozomunda bulunan ve FMRP proteininin sentezinden sorumlu olan FMR1 geninin sessizle\u015ftirilmesi sonucunda ortaya \u00e7\u0131kmaktad\u0131r. Hagerman, Amiri ve Cronister taraf\u0131ndan \u00f6zetlenmi\u015f Fragile X i\u00e7in yayg\u0131n olan \u00f6zellikleri aras\u0131nda zeka gerili\u011fi, hiperaktivite, dikkat s\u00fcresinin k\u0131salmas\u0131 gibi durumlar bulunmaktad\u0131r\u00a0(Hagerman et al., 1991). Bu hastal\u0131k, en s\u0131k g\u00f6r\u00fclen kal\u0131tsal zek\u00e2 gerili\u011fi sendromudur\u00a0(Huber et al., 2002). FMR1 geni 1991 y\u0131l\u0131nda tan\u0131mlanm\u0131\u015f\u00a0(Fern\u00e1ndez et al., 2013)\u00a0ve o g\u00fcnden bu yana hem eksikli\u011finden ortaya \u00e7\u0131kan bu hastal\u0131k hem de \u00fcretti\u011fi proteinin i\u015flevi ve yer ald\u0131\u011f\u0131 yolaklar hakk\u0131nda bir\u00e7ok ara\u015ft\u0131rma yap\u0131lm\u0131\u015ft\u0131r. Bu gen b\u00f6lgesinde bulunan CGG dizisinin tekrar say\u0131s\u0131n\u0131n artmas\u0131yla FMRP (\u2018Fragile X Mental Retardation Protein\u2019) sentezi de\u011fi\u015fime u\u011framaktad\u0131r. Bu ayki yaz\u0131mda sizlere Fragile X Sendromu ve alt\u0131nda yatan nedenler hakk\u0131nda bilgi vermeye \u00e7al\u0131\u015faca\u011f\u0131m.\u00a0<\/p>\n\n\n\n

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\u015eekil 1.
\u00a0https:\/\/www.the-scientist.com\/magazine-issue\/infographic–the-genetics-of-fragile-x-syndrome-66315<\/a><\/figcaption><\/figure>\n\n\n\n

FMR1 Geni ve FMRP<\/strong><\/h2>\n\n\n\n

FMR1 genindeki CGG tekrar say\u0131s\u0131 artt\u0131\u011f\u0131nda, Genel olarak bu hastal\u0131kla ili\u015fkilendirilen FMR1 geni mutasyonu -yaz\u0131m\u0131n en ba\u015f\u0131nda belirtti\u011fim gibi- CGG tekrar say\u0131s\u0131n\u0131n artmas\u0131 olsa da gen i\u00e7indeki farkl\u0131 mutasyonlar (\u00f6rne\u011fin nokta mutasyonlar\u0131) da bu hastal\u0131\u011f\u0131n ortaya \u00e7\u0131kmas\u0131na neden olabilir\u00a0(Handt et al., 2014). Bu nedenle sadece CGG tekrar testleriyle de\u011fil, daha nadir olsalar da di\u011fer mutasyonlar\u0131n kontrol edilmesiyle birlikte genetik testlerin y\u00fcr\u00fct\u00fclmesi ve bu \u015fekilde do\u011fru te\u015fhisin konulabilmesi \u00f6nerilmektedir\u00a0(Garber et al., 2008). CGG tekrar say\u0131s\u0131na g\u00f6re mutasyon tipleri de s\u0131n\u0131fland\u0131r\u0131lmaktad\u0131r. Genel olarak 5-44 tekrar aras\u0131 normal, 45-54 orta d\u00fczey, 55-200 aras\u0131 premutasyon, 200\u2019den fazla tekrar ise tam mutasyon olarak incelenmektedir\u00a0(Amerika Birle\u015fik Devletleri Hastal\u0131k Koruma ve \u00d6nleme Merkezi, 2020). FMR1 genindeki bu 3 n\u00fckleotid dizisinin tekrar say\u0131s\u0131ndaki art\u0131\u015f, FMRP \u00fcretimini de gen sessizle\u015ftirme mekanizmalar\u0131ndan dolay\u0131 engellemektedir\u00a0(Kaufmann et al., 2002). Premutasyon ta\u015f\u0131y\u0131c\u0131lar\u0131n\u0131n sa\u011fl\u0131k durumlar\u0131 hakk\u0131nda ara\u015ft\u0131rmalar hala devam etmektedir ancak bu durum genelde premat\u00fcr over yetmezli\u011fi veya FXTAS (Fragile-X Associated Tremor\/Ataxia Syndrome-Fragile X\u2019e Ba\u011fl\u0131 Tremor\/Ataksi Sendromu) gibi durumlarla ili\u015fkilendirilmektedir\u00a0(Allen et al., 2018). Fragile X kal\u0131tsal oldu\u011fundan premutasyon ta\u015f\u0131y\u0131c\u0131lar\u0131 da hastan\u0131n ailesinde yayg\u0131nd\u0131r.\u00a0<\/p>\n\n\n\n

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\u015eekil 2. Fragile X Sendromu\u2019nun kal\u0131t\u0131m\u0131n\u0131 g\u00f6steren bir diyagram. Premutasyon ta\u015f\u0131yan ebeveynin \u00e7ocuklar\u0131nda tam mutasyon olu\u015fabildi\u011fi de g\u00f6sterilmektedir.
https:\/\/fragilex.org\/education\/how-is-fragile-x-syndrome-inherited\/#iLightbox[4b79e7c8025a9053215]\/0<\/a><\/figcaption><\/figure>\n\n\n\n

FMR1 geni, v\u00fccutta bir\u00e7ok farkl\u0131 dokuda bulunabilen ve i\u015flevini g\u00f6steren FMRP adl\u0131 bir proteinin \u00fcretiminden sorumludur. Bu genin beyinde sinir h\u00fccreleri aras\u0131ndaki ba\u011flant\u0131lar\u0131n kurulmas\u0131nda ve geli\u015ftirilmesinde rol oynayabilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir (FMR1 Gene: MedlinePlus Genetics<\/em>, 2020). Beyindeki bu b\u00f6lgelerin ki\u015finin hayat\u0131 boyunca de\u011fi\u015fmesi ve duruma adapte olabilmesi, \u00f6\u011frenme s\u00fcre\u00e7lerini ve haf\u0131zay\u0131 m\u00fcmk\u00fcn k\u0131lmaktad\u0131r. FMRP proteini, mRNA translasyonunun \u00f6nemli bir denetleyicisi olarak sinaptik plastisite \u00f6zelli\u011finde belirleyicidir. Ayr\u0131cahem ba\u015fka proteinler arac\u0131l\u0131\u011f\u0131yla hem de RNA ba\u011flayan k\u0131s\u0131mlar\u0131 sayesinde mRNA\u2019larla etkile\u015fimde bulunabilmektedir (Sidorov et al., 2013). Bu proteinin aktivitesi ise fosforilasyonla kontrol edilebilmektedir. Fosforilasyon, FMRP\u2019nin ribozomlarda ger\u00e7ekle\u015fen translasyon s\u00fcrecini engellemesine neden olurken defosforilasyon tam tersine bu proteinin translasyonunu art\u0131rmas\u0131yla ili\u015fkilidir (Ceman et al., 2003). Dolay\u0131s\u0131yla, FMRP do\u011fru miktarda \u00fcretilmedi\u011finde h\u00fccrede rol oynad\u0131\u011f\u0131 bu \u00f6nemli metabolik yolaklar da zarar g\u00f6rmektedir. <\/p>\n\n\n\n

Tedavi \u00dczerine Ara\u015ft\u0131rmalar<\/strong><\/h2>\n\n\n\n

Fragile X Sendromu, hem kal\u0131tsal zek\u00e2 gerili\u011fi alt\u0131nda s\u0131n\u0131fland\u0131r\u0131lan hastal\u0131klar aras\u0131nda \u00e7ok yayg\u0131n olan hem de tedavi ara\u015ft\u0131rmalar\u0131 \u00e7ok kompleks olan bir hastal\u0131kt\u0131r. \u015eu anda sadece g\u00f6sterilen belirtilerin iyile\u015ftirilmesine odaklanmay\u0131p molek\u00fcler hedeflerle hastal\u0131\u011f\u0131n verece\u011fi zarar\u0131n \u00f6n\u00fcne ge\u00e7meye \u00e7al\u0131\u015fan ara\u015ft\u0131rmalar y\u00fcr\u00fct\u00fclmektedir. Bu konu \u00fczerinde \u00e7al\u0131\u015fan en \u00f6nemli kurumlardan biri de University of California Davis\u2019te bulunan MIND Enstit\u00fcs\u00fcd\u00fcr. Enstit\u00fcde bulunan Fragile X Ara\u015ft\u0131rma ve Tedavi Merkezi, 2001 y\u0131l\u0131nda Dr. Randi Hagerman liderli\u011finde kurulmu\u015ftur (UC Davis MIND Institute, n.d.). Y\u00fcr\u00fct\u00fclmekte olan \u00e7al\u0131\u015fmalar hakk\u0131nda bilgi almak i\u00e7in kaynak\u00e7amda da bulunan internet sitesini ziyaret edebilirsiniz.<\/p>\n\n\n\n

Kaynak\u00e7a<\/strong><\/h2>\n\n\n\n

Allen, E. G., Glicksman, A., Tortora, N., Charen, K., He, W., Amin, A., Hipp, H., Shubeck, L., Nolin, S. L., & Sherman, S. L. (2018). FXPOI: Pattern of AGG Interruptions Does not Show an Association With Age at Amenorrhea Among Women With a Premutation. Frontiers in Genetics<\/em>, 9<\/em>(AUG), 292. https:\/\/doi.org\/10.3389\/fgene.2018.00292<\/p>\n\n\n\n

Amerika Birle\u015fik Devletleri Hastal\u0131k Koruma ve \u00d6nleme Merkezi. (2020). How Fragile X Syndrome is Inherited | CDC<\/em>. https:\/\/www.cdc.gov\/ncbddd\/fxs\/inherited.html<\/p>\n\n\n\n

Ceman, S., O\u2019Donnell, W. T., Reed, M., Patton, S., Pohl, J., & Warren, S. T. (2003). Phosphorylation influences the translation state of FMRP-associated polyribosomes. Human Molecular Genetics<\/em>, 12<\/em>(24), 3295\u20133305. https:\/\/doi.org\/10.1093\/hmg\/ddg350<\/p>\n\n\n\n

Fern\u00e1ndez, E., Rajan, N., & Bagni, C. (2013). The FMRP regulon: From targets to disease convergence. In Frontiers in Neuroscience<\/em> (Vol. 7, Issue 7 OCT, p. 191). Frontiers. https:\/\/doi.org\/10.3389\/fnins.2013.00191<\/p>\n\n\n\n

FMR1 gene: MedlinePlus Genetics<\/em>. (n.d.). Retrieved December 4, 2020, from https:\/\/medlineplus.gov\/genetics\/gene\/fmr1\/<\/p>\n\n\n\n

Garber, K. B., Visootsak, J., & Warren, S. T. (2008). Fragile X syndrome. European Journal of Human Genetics<\/em>, 16<\/em>(6), 666\u2013672. https:\/\/doi.org\/10.1038\/ejhg.2008.61<\/p>\n\n\n\n

Hagerman, R. J., Amiri, K., & Cronister, A. (1991). Fragile X checklist. American Journal of Medical Genetics<\/em>, 38<\/em>(2\u20133), 283\u2013287. https:\/\/doi.org\/10.1002\/ajmg.1320380223<\/p>\n\n\n\n

Handt, M., Epplen, A., Hoffjan, S., Mese, K., Epplen, J. T., & Dekomien, G. (2014). Point mutation frequency in the FMR1 gene as revealed by fragile X syndrome screening. Molecular and Cellular Probes<\/em>, 28<\/em>(5\u20136), 279\u2013283. https:\/\/doi.org\/10.1016\/j.mcp.2014.08.003<\/p>\n\n\n\n

Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002). Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proceedings of the National Academy of Sciences of the United States of America<\/em>, 99<\/em>(11), 7746\u20137750. https:\/\/doi.org\/10.1073\/pnas.122205699<\/p>\n\n\n\n

Kaufmann, W. E., Cohen, S., Sun, H. T., & Ho, G. (2002). Molecular phenotype of fragile X syndrome: FMRP, FXRPs, and protein targets. In Microscopy Research and Technique<\/em> (Vol. 57, Issue 3, pp. 135\u2013144). Microsc Res Tech. https:\/\/doi.org\/10.1002\/jemt.10066<\/p>\n\n\n\n

Sidorov, M. S., Auerbach, B. D., & Bear, M. F. (2013). Fragile X mental retardation protein and synaptic plasticity. In Molecular Brain<\/em> (Vol. 6, Issue 1, pp. 1\u201311). BioMed Central. https:\/\/doi.org\/10.1186\/1756-6606-6-15<\/p>\n\n\n\n

UC Davis MIND Institute. (n.d.). Fragile X Research and Treatment Center: UC Davis MIND Institute<\/em>. Retrieved December 8, 2020, from https:\/\/health.ucdavis.edu\/mindinstitute\/research\/fragilex\/index.html<\/p>\n","protected":false},"excerpt":{"rendered":"

Fragile X Sendromu, X kromozomunda bulunan ve FMRP proteininin sentezinden sorumlu olan FMR1 geninin sessizle\u015ftirilmesi sonucunda ortaya \u00e7\u0131kmaktad\u0131r. Hagerman, Amiri<\/p>\n","protected":false},"author":273,"featured_media":8873,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[1478,1479,1475,1473,1228,115,1124,956,283,1477],"acf":[],"views":1372,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8870"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/273"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=8870"}],"version-history":[{"count":1,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8870\/revisions"}],"predecessor-version":[{"id":8874,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8870\/revisions\/8874"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/8873"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=8870"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=8870"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=8870"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}