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Lindsay-CashFragile X Mental Retardation Protein (FMRP)
CONTENTS
I. Translation The biological mechanism which the Fragile X Mental Retardation Protein (FMRP) participates in is translation. Translation is the process by which proteins are synthesized from mRNA. This process occurs on ribosomes via the linking of amino acids in the specific order indicated by the mRNA codons.[1] Translation consists of three steps: initiation, elongation, and termination. For a brief video overview of translation, see From RNA to Protein Synthesis. A study performed in 2000 by Laggerbauer et. al illustrated that in the absence of FMRP, translation of mRNA is drastically inhibited, manifesting in a vast array of biological problems in Fragile X Syndrome patients. Additionally, an article published by Eberhart et. al suggests that it is the alteration of FMRP binding transcripts which results in Fragile X Syndrome. For further information on the interference of translation click here.
II. FMRP A. FMR-1 gene 1. Location: The FMR-1 gene which is mutated resulting in Fragile X Syndrome is located on the X chromosome.
Image courtesy of www.google.com
2. Mutation: Fragile X Syndrome is caused by a mutation on the X chromosome at the FMR-1 gene. In people without this disorder, the FMR-1 gene generally has around 30 copies of a CGG repeated sequence. However, in individuals afflicted with Fragile X Syndrome, upwards of 200 repeats of the sequence are observed. When such a large number of copies are present, all the cytosines become methylated, silencing FMR-1 and preventing the production of the Fragile X Mental Retardation Protein (FMRP). Deactivation of FMR-1 and lack of production of FMRP has a chain reaction in the body due to the fact that FMRP is likely to be involved with the production of other proteins necessary for proper functioning (www.ygyh.com).
Image courtesy of www.fragilex.org
B. Function:
The FMRP protein is involved in neural synapse activity in the body. FMRP forms dimers in the cytoplasm of neurons and subsequently moves into the nucleus of these neurons. FMRP then forms a complex and is transported back into the cytoplasm of the neuron in order to regualte the synthesis of other proteins (www.nature.com).
C. Inheritance:
Inheritance of the FMR-1 gene is X-linked recessive. If the mother is a carrier and the father has a single correct copy of FMR-1, then offspring produced have the following statistical chances of getting Fragile X Syndrome:
Sons = 50% chance
Daughters: 50% chance
It should be noted that genetic testing to tell if someone is a carrier of the FMR-1 mutation resulting in Fragile X Syndrome is available (www.genetics.com).
Image courtesy of www.fraxa.org
III. FMRP Structure Below, images of the FMRP Protein are displayed. A study performed by Adinolfi et. al gave evidence for the existence of four regions in the FMR-1 gene itself. These regions consisted of a N-terminal stretch of 200 amino acids, two KH regions, and a C-terminal stretch. Binding of RNA occurs at one of the KH regions (www.rnajournal.cshlp.org).
Image courtesy of www.sueblimely.com Image courtesy of www.fragilex.org IV. Fragile X Syndrome
A. Description: Fragile X Syndrome is an inheritable disorder commonly referred to as mental retardation which is produced by a mutation on the FMR-1 gene (Fragile X Mental Retardation 1 gene) located on the X-chromosome (www.fragilex.org).
B. Statistics: Fragile X Syndrome is estimated to occur in 1/4000 males and 1/7000 females. Females with the FMR-1 gene mutation causing this disorder typically have symptoms which are less severe than those afflicting males (www.cdc.gov).
C. Characteristics: The characteristics of Fragile X Syndrome vary between males and females. Common features exhibited in those with this disorder are as follows:
Image courtesy of www.wafragilex.org Image courtesy of www.nfxf.org
D. Treatment: Due to the fact that Fragile X Syndrome is caused by a lack of FMRP production by the FMR-1 gene, there is currently no treatment available to cure Fragile X. In order to completely reverse the disorder, a treatment would have to be utilized which produced the FMRP protein. However, those suffering from Fragile X Syndrome are not hopeless. There are a wide variety of symptomatic treatments to help with traits such as speech impairment, hyperactivity, and behavior (www.ygyh.org).
E. Research: Below, several research projects conducted on Fragile X Syndrome are presented. For further information on a study, click the interactive links within the text.
1. mGluR5 gene research: The Fragile X Mental Retardation protein serves an important purpose in regulating the activity of the mGluR5 gene. The mGluR5 gene's role in the body is to generate neural synapses. This production of synpases is controlled by FMRP in unafflicted individuals. However, in those beings which lack proper FMRP production, an overproduction of synapses occurs. Therefore, the production of receptor drugs which reduce mGlueR5's signaling, returns normal synapse balance in the absence of FMRP(The Dana Foundation, 2008).
2. Gene Therapy: This mode of research aims to address the possibility of being able to insert a FMR-1 gene which lacks the Fragile X mutation into a person afflicted with Fragile X Syndrome in order to substitute a healthy copy of the gene for the mutated gene (www.fragilex.org).
3. Protein Replacement:Protein replacement research centers around the idea of being able to incorporate the FMRP protein from an alternative source to counteract the lack of production in Fragile X patients (www.fragilex.org).
4. Medication: Medications utilized to reduce hyperactivity and anxiety are reported to help 90% of Fragile X children (www.ygyh.com).
F. Living with Fragile X Syndrome: Most people are unaware of what life with Fragile X Syndrome is truly like unless they have a loved one afflicted with this disorder. The video below was produced by the FRAXA Fragile X Research Foundationin an effort to educate people about how this disease affects the daily life of both those afflicted and their caregivers, in addition to some of the research being currently performed on this disorder.
Footnotes
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Comments (1)
Christopher Korey said
at 4:12 pm on Apr 6, 2009
This looks really great. I love all of the other sites you have found. I think the best way to incorporate them is to write concise text that gives a basic information and then provides a link out to the more detailed information. For example, give a basic run down of the disease and its clinical manifestations, but then link out to video or places like OMIM that provide a more detailed description for those who want it. I haven't been able to fina a great image or structure for the protein either so its okay to not include one or go with the one you have. Make sure to reference in the text and use the footnoting. Great Job.
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