Talk:Fragile X Syndrome: Difference between revisions
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PMID 22797890 | PMID 22797890 | ||
===Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome=== | |||
Neural Plast. 2012;2012:104796. Epub 2012 Jun 20. | |||
Kelley K, Chang SJ, Lin SL. | |||
Source | |||
Division of Regenerative Medicine, WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, STE6, Santa Fe Springs, CA 90670, USA. | |||
Abstract | |||
The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs) such as fragile X syndrome (FXS). After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA)-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs) is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5'-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR)-activated long-term depression (LTD), leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention. | |||
PMID 22779005 | |||
http://www.hindawi.com/journals/np/2012/104796/ | |||
Revision as of 15:43, 20 July 2012
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Cite this page: Hill, M.A. (2024, May 1) Embryology Fragile X Syndrome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Fragile_X_Syndrome |
2012
Genetic Counseling and Testing for FMR1 Gene Mutations: Practice Guidelines of the National Society of Genetic Counselors
J Genet Couns. 2012 Jul 14. [Epub ahead of print]
Finucane B, Abrams L, Cronister A, Archibald AD, Bennett RL, McConkie-Rosell A. Source
Genetic Services at Elwyn, Elwyn, PA, USA, brenda_finucane@elwyn.org.
Abstract
Fragile X syndrome (FXS) is one of several clinical disorders associated with mutations in the X-linked Fragile X Mental Retardation-1 (FMR1) gene. With evolving knowledge about the phenotypic consequences of FMR1 transcription and translation, sharp clinical distinctions between pre- and full mutations have become more fluid. The complexity of the issues surrounding genetic testing and management of FMR1-associated disorders has increased; and several aspects of genetic counseling for FMR1 mutations remain challenging, including risk assessment for intermediate alleles and the widely variable clinical prognosis for females with full mutations. FMR1 mutation testing is increasingly being offered to women without known risk factors, and newborn screening for FXS is underway in research-based pilot studies. Each diagnosis of an FMR1 mutation has far-reaching clinical and reproductive implications for the extended family. The interest in large-scale population screening is likely to increase due to patient demand and awareness, and as targeted pharmaceutical treatments for FXS become available over the next decade. Given these developments and the likelihood of more widespread screening, genetic counselors across a variety of healthcare settings will increasingly be called upon to address complex diagnostic, psychosocial, and management issues related to FMR1 gene mutations. The following guidelines are intended to assist genetic counselors in providing accurate risk assessment and appropriate educational and supportive counseling for individuals with positive test results and families affected by FMR1-associated disorders.
PMID 22797890
Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome
Neural Plast. 2012;2012:104796. Epub 2012 Jun 20.
Kelley K, Chang SJ, Lin SL. Source
Division of Regenerative Medicine, WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, STE6, Santa Fe Springs, CA 90670, USA.
Abstract
The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs) such as fragile X syndrome (FXS). After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA)-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs) is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5'-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR)-activated long-term depression (LTD), leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.
PMID 22779005
