Fragile X protein linked to nearly 100 genes involved in autism

December 12, 2012

Doctors have known for many years that patients with fragile X syndrome, the most common form of inherited intellectual disability, are often also diagnosed with autism. But little has been known about how the two diagnoses are related.

Now a collaborative research effort at Duke University Medical Center and Rockefeller University has pinpointed the precise footprint that links the two. The findings, published online in the journal Nature on Dec. 12, 2012, point the way toward new genetic testing that could more precisely diagnose and categorize the spectrum of autism-related disorders.

is the most well understood single-gene cause of autism. It results from defects on a small part of the for a that researchers have dubbed the fragile X mental retardation protein, or FMRP.

Normally, FMRP plays an important role controlling production of other and other organs. It does this by looking for specific genetic patterns located on the messages encoding proteins. When it locates these genetic flags, it attaches to them and, along with other signals, controls where and when protein is made.

In fragile X syndrome, this process breaks down because a defect in the gene causes the body to produce too little, or in some cases, none of the FMRP protein. As a result, additional proteins it would normally regulate are made in the wrong place and at the wrong time. Until now, little was known about how this process worked in people with the autism.

Using a combination of and advanced bioinformatics, the research team, led by Thomas Tuschl, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, and Uwe Ohler, PhD, an associate professor in Biostatistics and Bioinformatics at the Duke Institute for & Policy, identified both the genetic flags that FMRP is looking for and the genes it targets.

The researchers discovered that FMRP directly controls at least 93 genes that have been independently linked to autism, as well as Angelman, Prader-Willi, Rett and other neurologic syndromes that have overlapping features with autism.

Additional research using a mouse model of fragile X syndrome revealed that the animals had abnormal protein production not only in the brain, but also in the ovary. The findings confirmed that the absence of FMRP protein causes ovarian insufficiency, which is common among women affected by fragile x syndrome.

"We now know not only which genes are linked to FMRP, but we can locate exactly where they interact," said Ohler. "Down the road, this finding could lead to more detailed genetic tests that take into account the subtle ways that genes get turned on and off."

Physicians who work with fragile X patients know that each patient's abilities and challenges are unique. Some individuals have almost no disability, while others have more severe physical and intellectual disabilities. Approximately 2 percent to 6 percent of children with autism are also diagnosed with fragile X and about one-third of fragile X patients also meet the criteria for autism.

The new discovery should now enable researchers to examine the common molecular pathways leading to all forms of autism. Identification of those pathways could also lead to more targeted treatments for both fragile x and autism.

"We can now look for changes in the FMRP binding sites of genes to identify potential new genetic links to autism-spectrum disorders," said Neelanjan Mukherjee, a Duke post-doctoral scientist who contributed to the research.

Explore further: Workings of brain protein suggest therapies for inherited intellectual disability, autism

Related Stories

Workings of brain protein suggest therapies for inherited intellectual disability, autism

July 21, 2011
Researchers now have a much clearer understanding of how mutations in a single gene can produce the complex cognitive deficits characteristic of Fragile X Syndrome, the most common inherited form of intellectual disability. ...

New clue found for Fragile X syndrome-epilepsy link

April 12, 2011
Individuals with fragile X syndrome, the most common inherited form of intellectual disability, often develop epilepsy, but so far the underlying causes are unknown. Researchers have now discovered a potential mechanism that ...

Evolution's gift may also be at the root of a form of autism

May 10, 2012
A recently evolved pattern of gene activity in the language and decision-making centers of the human brain is missing in a disorder associated with autism and learning disabilities, a new study by Yale University researchers ...

Fragile X and Down syndromes share signalling pathway for intellectual disability

August 3, 2012
Intellectual disability due to Fragile X and Down syndromes involves similar molecular pathways report researchers in The EMBO Journal. The two disorders share disturbances in the molecular events that regulate the way nerve ...

Recommended for you

Gene variant activity is surprisingly variable between tissues

August 21, 2017
Every gene in almost every cell of the body is present in two variants called alleles—one from the mother, the other one from the father. In most cases, both alleles are active and transcribed by the cells into RNA. However, ...

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.