Back متلازمة الرعاش والرنح المرتبطة بالصبغي إكس الهش Arabic Síndrome d'atàxia i tremolor associada a X fràgil Catalan Fragiles-X-assoziiertes Tremor-/Ataxie-Syndrom German FXTAS Swedish

Fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome
Abbreviation: FXTAS
Pronunciation: "FAX-tass"[1]
Location of the FMR1 gene
Location of the FMR1 gene
Location of the FMR1 gene
Specialty: Neurology, Movement Disorders
Symptoms: intention tremor, ataxia, and parkinsonism
Prevalence: In patients over 50 with FMR1 premutation:
Onset: Late-onset, diagnosed in patients >50 years[1]
Diagnosis: Presentation, family history, genetic testing, and MRI

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder most frequently seen in male premutation carriers of Fragile X syndrome (FXS) over the age of 50.[4][5] The main clinical features of FXTAS include problems of movement with cerebellar gait ataxia and action tremor.[4][6] Associated features include parkinsonism, cognitive decline, and dysfunction of the autonomic nervous system.[4][6] FXTAS is found in Fragile X "premutation" carriers, which is defined as a trinucleotide repeat expansion of 55-200 CGG repeats in the Fragile X mental retardation-1 (FMR1) gene.[7] 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome.[7]

In contrast to FXS full mutation, which is diagnosed early in childhood, symptoms of FXTAS manifest in individuals over the age of 50.[1] Like FXS, FXTAS is most common and most severe in males due to the mutation's X-linked inheritance pattern.[2] FXTAS has an incidence of 30-40% (male) and 8-15% (female) among FXS premutation carriers over the age of 50.[2][3]

FMR1 mRNA is found to be elevated in patients with FXTAS[7] in contrast to FXS, where the FMR1 gene is transcriptionally silenced via DNA methylation.[8] In both diseases the FMR1 gene product, Fragile X mental retardation protein (FMRP) is diminished, but in FXTAS this is believed to be mediated by RNA toxicity, while in FXS, FMRP is absent due to transcriptional silencing.[7]

There is no cure for FXTAS, but several of the symptoms can be managed with medication.[7]

  1. ^ a b c "Fragile X-Associated Tremor and Ataxia Syndrome (FXTAS): Overview". www.nichd.nih.gov. Retrieved 2017-07-07.
  2. ^ a b c d Saul, Robert A.; Tarleton, Jack C. (1993). "FMR1-Related Disorders". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Ledbetter, Nikki; Mefford, Heather C. (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301558.
  3. ^ a b c Jacquemont, Sébastien (2004-01-28). "Penetrance of the Fragile X–Associated Tremor/Ataxia Syndrome in a Premutation Carrier Population". JAMA. 291 (4): 460–469. doi:10.1001/jama.291.4.460. ISSN 0098-7484. PMID 14747503.
  4. ^ a b c Wheeler, Anne; Raspa, Melissa; Hagerman, Randi; Mailick, Marsha; Riley, Catharine (2017-06-01). "Implications of the FMR1 Premutation for Children, Adolescents, Adults, and Their Families". Pediatrics. 139 (Supplement 3): S172–S182. doi:10.1542/peds.2016-1159D. ISSN 0031-4005. PMC 5621635. PMID 28814538.
  5. ^ Tassone, Flora; Berry-Kravis, Elizabeth M, eds. (2010). The fragile X-associated tremor ataxia syndrome (FXTAS). Springer New York. doi:10.1007/978-1-4419-5805-1. ISBN 9781441958051.
  6. ^ a b Leehey, M. A.; Berry-Kravis, E.; Goetz, C. G.; Zhang, L.; Hall, D. A.; Li, L.; Rice, C. D.; Lara, R.; Cogswell, J. (2008-04-15). "FMR1 CGG repeat length predicts motor dysfunction in premutation carriers". Neurology. 70 (16 Pt 2): 1397–1402. doi:10.1212/01.wnl.0000281692.98200.f5. ISSN 1526-632X. PMC 2685188. PMID 18057320.
  7. ^ a b c d e Kong, Ha Eun; Zhao, Juan; Xu, Shunliang; Jin, Peng; Jin, Yan (2017-05-05). "Fragile X-Associated Tremor/Ataxia Syndrome: From Molecular Pathogenesis to Development of Therapeutics". Frontiers in Cellular Neuroscience. 11: 128. doi:10.3389/fncel.2017.00128. ISSN 1662-5102. PMC 5418347. PMID 28529475.
  8. ^ Colak, Dilek; Zaninovic, Nikica; Cohen, Michael S.; Rosenwaks, Zev; Yang, Wang-Yong; Gerhardt, Jeannine; Disney, Matthew D.; Jaffrey, Samie R. (2014-02-28). "Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome". Science. 343 (6174): 1002–1005. Bibcode:2014Sci...343.1002C. doi:10.1126/science.1245831. ISSN 1095-9203. PMC 4357282. PMID 24578575.

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