What is a Possible Cause of Autism?

In doing a little digging about autism and myotonic dystrophy, Fragile X is a disease that pops right to the top of the screen. This is also a triplet expansion disease and it has a couple of similarities especially to some of the childhood forms of myotonic dystrophy. Fragile x causes mental retardation (Global developmental delay) as well as many of the kids have Autism or Autism spectrum disorder. Here is a review of Autism and Fragile X

Fragile X and Autism-related Disorders Click here for full program
From Basic Neuroscience to Improved Clinical Care
June 10-15, 2012
Stonehill College
Easton, MA
Chair:
Elizabeth M. Berry-Kravis Vice Chair:
Jennifer C. Darnell

Fragile X syndrome (FXS) is the most common form of inherited intellectual deficiency and the most common identifiable single gene cause of autism, affecting 1 in 5,000 males and a lesser number of females. Autism spectrum disorders (ASD) occur in up to 2/3 of males and 1/3 of females with FXS. The Fragile X gene (FMR1) was cloned in 1991 and since then a large field has grown with roughly one hundred labs using techniques from biochemistry through genetics to model organisms to elucidate the functions of the FMR1 protein (FMRP). FMR1 gene homologs have been found in Drosophila and mice, and useful null mutant models generated in both. FMRP has been found to be involved in the regulation of specific messenger RNA transport, localization and expression in neurons. Briefly put, FMRP is thought to bind and help transport a crucial subset of messages to the sites of neural action (the synapses). At those synapses, FMRP is a critical switch that mediates changes in local protein expression in response to neural activity – in effect causing the synapses to strengthen or weaken as required in response to experience. When FMRP is reduced or missing in an affected person, the synapses are much less able to change with experience and learning is greatly reduced. More recently, specific signaling mechanisms have been proposed to mediate this control at the synapse, via a specific set of Gq-linked (neurotransmitter) receptors, including group I mGluRs (metabotropic glutamate receptors). It has become clear that in addition to clinical overlap between FXS and ASD, there is likely substantial overlap in the molecular pathology of the two disorders. As such, molecular defects known to cause ASD may involve other proteins in the signaling pathways that are regulated by or regulate FMRP activity, may involve proteins for which synaptic translation is regulated by FMRP, or may involve defects in neurotransmitter systems shown to be dysregulated in FXS models. Molecules aimed at targets in pathways that are dysregulated in the absence of FMRP are now being developed and tested in academic laboratories and through the pharmaceutical industry, in order to offer effective drug therapies for affected patients with FXS. It is expected that many of these targeted treatments will have therapeutic overlap in subsets of individuals with ASD.

This conference will bring together leading scientists and clinicians in the Fragile X and ASD fields. Topics will include molecular genetics, model system characterizations, synaptic signaling and function studies, small molecule trials and clinical reports.

This report and conference gives some clues as to what may cause autism in the childhood forms of myotonic dystrophy. We know what the cause is of myotonic dystrophy mis-regulation of the RNA’s cause them to clump in the nucleus of the cell causing foci (trapping proteins in the cell). In this report apparently there is some thought that proteins somehow are not doing the proper job in mediating the response from the synapses in the brain. The synapic response here is part of the learning in response to enviromental stimulus such as interactions with others, proper social behaviors, response to stimuli..

The above summary suggests that proteins from the brain cells are very important for the synapses (spaces between brain cells) to learn in response to experiences that the person has. When Childhood  Myotonic Dystrophy is present in an affected person, the synapses are much less able to change with experience and learning is greatly reduced. this last sentence is a proposed mechanism of action of autism in myotonic dystrophy and will need to be verified by researchers.

However, because the diseases are very close in the triplet expansion cause the mechanism of action may be close as well. Any help in moving forward

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