Tag Archives: Mutations

Question?: Rett Syndrome In Boys

Lisa asks…

what is Rett’s syndrome?

admin answers:

What is Rett syndrome?
Rett syndrome is a unique developmental disorder that is first recognized in infancy and seen almost always in girls, but can be rarely seen in boys. It is caused by mutations on the X chromosome on a gene called MECP2. There are more than 200 different mutations found on the MECP2 gene. Most of these mutations are found in eight different “hot spots.” It strikes all racial and ethnic groups, and occurs worldwide in 1 of every 10,000 to 23,000 female births.

Rett syndrome is a developmental disorder. It is not a degenerative disorder. It causes problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function. These can include learning, speech, sensory sensations, mood, movement, breathing, cardiac function, and even chewing, swallowing, and digestion.

Rett syndrome symptoms appear after an early period of apparently normal or near normal development until six to eighteen months of life, when there is a slowing down or stagnation of skills. A period of regression then follows when she loses communication skills and purposeful use of her hands. Soon, stereotyped hand movements such as handwashing, gait disturbances, and slowing of the normal rate of head growth become apparent. Other problems may include seizures and disorganized breathing patterns while she is awake. In the early years, there may be a period of isolation or withdrawal when she is irritable and cries inconsolably. Over time, motor problems may increase, but in general, irritability lessens and eye contact and communication improve.

Rett syndrome is confirmed with a simple blood test to identify the MECP2 mutation. However, since the MECP2 mutation is also seen in other disorders, the presence of the MECP2 mutation in itself is not enough for the diagnosis of Rett syndrome. Diagnosis requires either the presence of the mutation (a molecular diagnosis) or fulfillment of the diagnostic criteria (a clinical diagnosis, based on signs and symptoms that you can observe) or both.

Rett syndrome can present with a wide range of disability ranging from mild to severe. The course and severity of Rett syndrome is determined by the location, type and severity of her mutation and X-inactivation. Therefore, two girls of the same age with the same mutation can appear quite different.

Rett syndrome presents many challenges, but with love, therapy and assistance, those with the syndrome can benefit from school and community activities well into middle age and beyond. They experience a full range of emotions and show their engaging personalities as they take part in social, educational, and recreational activities at home and in the community.
Http://www.rettsyndrome.org/index.php?option=com_content&task=view&id=16&Itemid=1000

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Question?: Rett Syndrome Causes

Mark asks…

is rett syndrome caused by a single gene or more than one gene?

admin answers:

Its is hard to say, Please read the following it seems like a lot but it’ll give you a better idea:

Most cases of classic Rett syndrome are caused by mutations in the MECP2 gene. This gene provides instructions for making a protein (MeCP2) that is critical for normal brain development. The MeCP2 protein likely plays a role in forming connections (synapses) between nerve cells. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. The MeCP2 protein may also control the production of different versions of certain proteins in nerve cells. Although mutations in the MECP2 gene disrupt the normal function of nerve cells, it is unclear how these mutations lead to the signs and symptoms of Rett syndrome.

Males with mutations in the MECP2 gene often die before birth or in infancy. A small number of males with a MECP2 mutation, however, have developed signs and symptoms similar to those of classic Rett syndrome. Some of these boys have an extra X chromosome in many or all of the body’s cells. The extra X chromosome contains a normal copy of the MECP2 gene, which produces enough of the MeCP2 protein for the boys to survive. Other males with features of Rett syndrome have mutations in the MECP2 gene that occur after conception and are present in only a fraction of the body’s cells. In rare cases, researchers have discovered that the MECP2 gene is abnormally duplicated in boys with intellectual disability and some developmental problems characteristic of Rett syndrome.

Mutations in the CDKL5 gene cause an atypical form of Rett syndrome in females called the early-onset seizure variant. The CDKL5 gene provides instructions for making a protein that appears to be essential for normal brain development. Although the function of this protein is unknown, it may play a role in regulating the activity of other genes. Researchers are working to determine how mutations in the CDKL5 gene lead to seizures and the features of Rett syndrome in affected girls.

Also the following is what someone had written on the rettnet

“Rett syndrome is a clinical diagnosis. This means saying someone has Rett
syndrome depends on their clinical picture, regardless of whether a mutation is present or not. To determine whether a mutation is
responsible in your daughter would require one or both parents to be
tested looking specifically for the mutation. Typically one parent (either one) is tested first. If not found in the 1st parent, proceed to testing the 2nd parent. If a mutation is found in either parent, it is likely a polymorphism which is
a non-disease producing variation. If no mutation is found in eitherparent, then it likely to be signficant and responsible for whatever
difficulties she demonstrates. Again, Rett syndrome is a clinical diagnosis, so it is possible to have a non-polymorphism mutation in this
gene and not have Rett syndrome”

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Question?: Rett Syndrome Causes

Michael asks…

what is some current research for rett syndrome?

i’m writing it in my brochure and i can’t find it anywhere!

admin answers:

Here are some great facts! Brochures are great when they are loaded with lots of facts and graphics. Use some of these:

Rett syndrome is a unique developmental disorder that is first recognized in infancy and seen almost always in girls, but can be rarely seen in boys.

Rett syndrome has been most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay

Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. There are more than 200 different mutations found on the MECP2 gene. Most of these mutations are found in eight different “hot spots.”

Rett syndrome strikes all racial and ethnic groups, and occurs worldwide in 1 of every 10,000 to 23,000 female births.

Rett syndrome is a developmental disorder. It is not a degenerative disorder.

Rett syndrome causes problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function. These can include learning, speech, sensory sensations, mood, movement, breathing, cardiac function, and even chewing, swallowing, and digestion.

Rett syndrome symptoms appear after an early period of apparently normal or near normal development until six to eighteen months of life, when there is a slowing down or stagnation of skills. A period of regression then follows when she loses communication skills and purposeful use of her hands. Soon, stereotyped hand movements such as handwashing, gait disturbances, and slowing of the normal rate of head growth become apparent. Other problems may include seizures and disorganized breathing patterns while she is awake. In the early years, there may be a period of isolation or withdrawal when she is irritable and cries inconsolably. Over time, motor problems may increase, but in general, irritability lessens and eye contact and communication improve.

Rett syndrome is confirmed with a simple blood test to identify the MECP2 mutation. However, since the MECP2 mutation is also seen in other disorders, the presence of the MECP2 mutation in itself is not enough for the diagnosis of Rett syndrome. Diagnosis requires either the presence of the mutation (a molecular diagnosis) or fulfillment of the diagnostic criteria (a clinical diagnosis, based on signs and symptoms that you can observe) or both.

Rett syndrome can present with a wide range of disability ranging from mild to severe. The course and severity of Rett syndrome is determined by the location, type and severity of her mutation and X-inactivation. Therefore, two girls of the same age with the same mutation can appear quite different.

Rett syndrome presents many challenges, but with love, therapy and assistance, those with the syndrome can benefit from school and community activities well into middle age and beyond. They experience a full range of emotions and show their engaging personalities as they take part in social, educational, and recreational activities at home and in the community.

Good luck in your work! 🙂

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Question?: Rett Syndrome Causes

Chris asks…

Is rett syndrome caused by a non-disjunction?

-is it caused by a non-disjunction and how?
-is it a sex-linked and if so then why or how?
-is it autosomal and if so then why or how?

admin answers:

Classic Rett syndrome has an X-linked dominant pattern of inheritance.
The vast majority of cases of classic Rett syndrome are caused by mutations in the MECP2 gene.

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Question?: Autism Signs And Symptoms

Ruth asks…

Do you think that the increase in autism in the 90’s was because of the increase in immunizations?

In the 80’s baby’s were given 12 injections their first year of life.
The number of injections increased almost tripled in the 90’s.
Do you think its more environmental causes for autism or from the immunizations?

admin answers:

In my opinion, vaccines aren’t the only thing that is going on with children and autism. We didn’t “have” autism years ago, because no one really new about it. It is the same as depression or ADD years ago. As people change, so do the things that effect them. Science is constantly looking at things and finding new things that we never new about.
I also think that vaccines are something that sets off a reaction in the body. If you have an understanding on how vaccines work and also how your immune system works, you will understand how everything down to cancer starts and stops in your body. Whenever you add a foreign body into the blood (or any type of barrier), you will have an effect. Immunizations are helpful, but the way that they are done and the amount that is required is horrendous. Lets me ask you all something…..if you were immunized as a child, do you get your booster shots? Alot of them need to be re administered or they aren’t effective…what’s the point? Also, do you know what is in those shots? Formaldyde is used as a cross link for some to the chemicals……would you even put that on your SKIN for any reason?

So …..do they CAUSE autism….probably not. Do they do things to the body to set off the signs and symptoms, yup! As we increase what you inject into a tiny immune system, the mutations show readily. Just as we have been adding growth hormones to our meat, now our children are developing faster and sooner.

To above, thimerosal is still in vaccines (check your flu vaccine), they took it out of a couple because of the pressure behind what has been brought forward.

I’m not pushing my beliefs. I am a nursing student and I can tell you first hand that we all need to question our what is going on in the health care field. It almost all revolves around money here in the states….thanks for reading my rant!

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Question?: Rett Syndrome Genetics

John asks…

Question about the genetics behind Treacher-Collins Syndrome?

From what I understand, in order for a person to have Treacher-Collins Syndrome they have to have at least one dominant gene for Treacher-Collins Syndrome. If this is true, then if someone has the gene for Treacher-Collins Syndrome that can be passed down to their child, then they themselves have to have the syndrome. If this is true, then how can two people, who do not have Treacher-Collins Syndrome or the gene that causes it, have a child who does have the syndrome? (The example that I’m referencing is Juliana Wetmore.)

admin answers:

There was a new mutation. It could be that the mutation happened in the sperm or egg, or that the mutation occurred in the zygote in the first few days after conception.

All of us have mutations in at least a few genes, genes that are anywhere from slightly different to our parents’, to missing or doubled.
Chromosomal abnormalities (Down Syndrome, Turner Syndrome, Edward Syndrome, Klinefelter’s), achondroplastic dwarfism, Rett Syndrome, are all examples of conditions where there is most often a new mutation causing it.

Other disorders have “premutations” where a gene becomes unstable and then starts mutating in further generations- the genes for Huntington’s Chorea (which gets worse and worse in subsequent generations), and Fragile X are like that.

Most autosomal dominant disorders are fairly uncommon because of the rate of new mutations.

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Boys More Affected By Mutations In Autism Susceptibility Gene

Main Category: Autism
Also Included In: Genetics;  Men’s Health
Article Date: 15 Jul 2012 – 0:00 PDT Current ratings for:
Boys More Affected By Mutations In Autism Susceptibility Gene
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Researchers at Emory University School of Medicine have identified five rare mutations in a single gene that appear to increase the chances that a boy will develop an autism spectrum disorder (ASD).

Mutations in the AFF2 gene, and other genes like it on the X chromosome, may explain why autism spectrum disorders affect four times as many boys as girls.

The mutations in AFF2 appeared in 2.5 percent (5 out of 202) boys with an ASD. Mutations in X chromosome genes only affect boys, who have one X chromosome. Girls have a second copy of the gene that can compensate.

The results were published in the journal Human Molecular Genetics.

“Our data suggest that AFF2 could be one of the major X-linked risk factors for ASD’s,” says senior author Michael Zwick, PhD, assistant professor of human genetics at Emory University School of Medicine.

The finding bolsters a growing consensus among geneticists that rare variants in many different genes contribute significantly to risk for autism spectrum disorders.

The mutations in the AFF2 gene probably do not cause ASDs all by themselves, Zwick says.

“We do not think that the variants we have identified are monogenic causes of autism,” he says. “Our data does support the idea that this is an autism susceptibility gene.”

In some situations, mutations in a single gene are enough by themselves to lead to a neurodevelopmental disorder with autistic features, such as fragile X syndrome or tuberous sclerosis complex. But these types of mutations are thought to account for a small number of ASD cases.

Recent large-scale genetic studies of autism spectrum disorders have identified several “rare variants” that sharply increase ASD risk. Scientists believe rare variants could explain up to 15 or 20 percent of ASD cases. However, until now no single variant has been found in more than one percent of ASD cases.

Working with Zwick, postdoctoral fellow Kajari Mondal and her colleagues read the sequence of the AFF2 gene in DNA from 202 boys diagnosed with autism spectrum disorders. The patient samples came from the Autism Genetic Resource Exchange and the Simons Simplex Collection.

Tests showed that in four cases, the affected boys had inherited the risk-conferring mutations from their mothers. One boy had a “de novo” (not coming from the parents) mutation. Compared with X-linked genes in unaffected people, mutations in AFF2 were five times more abundant in the boys with ASDs.

The AFF2 gene had already been identified as responsible for a rare inherited form of intellectual disability with autistic features. This effect is seen when the AFF2 gene is deleted or silenced completely.

AFF2 has some similarity to FMR1, the gene responsible for fragile X syndrome. Like FMR1, it can be silenced by a triplet repeat. In these cases, the presence of the triplet repeat (three genetic bases repeated dozens of times) triggers a change in chromosomal structure that prevents the gene from being turned on.

In contrast, the mutations Zwick’s team found are more subtle, slightly changing the sequence of the protein AFF2 encodes. Little is known about the precise function of the AFF2 protein. A related gene in fruit flies called lilliputian also appears to regulate the development of neurons.

Zwick says one of his laboratory’s projects is to learn more about the function of the AFF2 gene, and to probe how the mutations identified by his team affect the function. His team is also working on gauging the extent to which other genes on the X chromosome contribute to autism risk.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our autism section for the latest news on this subject. The research was supported by the National Institute of Mental Health (MH076439) and the Simons Foundation Autism Research Initiative.
Reference: K. Mondal, D. Ramachandran, V.C. Patel, K.R. Hagen, P. Bose, D.J. Cutler and M.E. Zwick. Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder. Hum. Mol. Genet. Advance access. (2012). doi: 10.1093/hmg/dds267
Emory University Please use one of the following formats to cite this article in your essay, paper or report:

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15 Jul. 2012. APA

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Enlarged Brain Size, Autism, Epilepsy And Cancer Linked To Newly Found Gene Mutations

Editor’s Choice
Main Category: Genetics
Also Included In: Neurology / Neuroscience;  Cancer / Oncology;  Autism
Article Date: 03 Jul 2012 – 11:00 PDT Current ratings for:
Enlarged Brain Size, Autism, Epilepsy And Cancer Linked To Newly Found Gene Mutations
3 and a half stars5 stars
According to a study published online in Nature Genetics, researchers have identified three new mutations associated with megalencephaly (enlarged brain size), cancer, autism, hydrocephalus, skin growth disorders, epilepsy, and vascular anomalies.

The study, led by Seattle Children’s Research Institute, provides further evidence that the genetic make-up of an individual is not entirely determined at the time of conception. Earlier studies have shown that genetic changes can also occur after conception. In addition, the teams finding may lead to the possibilities of new treatments for these diseases.

The researchers discovered mutations in three genes, AKT3, PIK3R2 and PIK3CA, all of which are present in humans. However, variations in these genes lead to a wide variety of disorders, including cancer, megalencephaly, and other disorders.

Previous studies have found an associated between the PIK3CA gene and cancer, and it appears that this gene is able to make cancer more aggressive.

James Olson, M.D., Ph.D., a pediatric cancer expert at Seattle Children’s and Fred Hutchinson Cancer Research Center who was not affiliated with the study, explained:

“This study represents ideal integration of clinical medicine and cutting-edge genomics. I hope and believe that the research will establish a foundation for successfully using drugs that were originally developed to treat cancer in a way that helps normalize intellectual and physical development of affected children.”

The team ‘knocked it out of the park’ by deep sequencing exceptionally rare familial cases and unrelated cases to identify the culprit pathway.”

AKT3, PIK3R2 and PIK3CA all encode core components of the phosphatidylinositol-3-kinase (P13K)/AKT pathway, the “culprit pathway” referenced by Olson.

The teams findings provide new insight into chronic childhood conditions and disease and could lead to new treatments within ten years.

William Dobyns, M.D., a geneticist at Seattle Children’s Research Institute, explained:

“This is a huge finding that provides not only new insight for certain brain malformations, but also, and more importantly, provides clues for what to look for in less severe cases and in conditions that affect many children.

Kids with cancer, for example, do not have a brain malformation, but they may have subtle growth features that haven’t yet been identified. Physicians and researchers can now take an additional look at these genes in the search for underlying causes and answers.”

The next step for the researchers is to investigate deeper into their findings and uncover even more about the potential medical implications for children.

Jean-Baptiste Rivière, PhD, at Seattle Children’s Research Institute, concluded:

“Based on what we’ve found, we believe that we can eventually reduce the burden of and need for surgery for kids with hydrocephalus and change the way we treat other conditions, including cancer, autism, and epilepsy. This research truly helps advance the concept of personalized medicine.”

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our genetics section for the latest news on this subject. “De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes “
Jean-Baptiste Rivière, Ghayda M Mirzaa, Brian J O’Roak, Margaret Beddaoui, Diana Alcantara, Robert L Conway, Judith St-Onge, Jeremy A Schwartzentruber, Karen W Gripp, Sarah M Nikkel, Thea Worthylake, Christopher T Sullivan, Thomas R Ward, Hailly E Butler, Nancy A Kramer, Beate Albrecht, Christine M Armour, Linlea Armstrong, Oana Caluseriu, Cheryl Cytrynbaum, Beth A Drolet, A Micheil Innes, Julie L Lauzon, Angela E Lin, Grazia M S Mancini et al.
Nature Genetics, June 2012, doi: 10.1038/ng.2331 Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Grace Rattue. “Enlarged Brain Size, Autism, Epilepsy And Cancer Linked To Newly Found Gene Mutations.” Medical News Today. MediLexicon, Intl., 3 Jul. 2012. Web.
5 Jul. 2012. APA

Please note: If no author information is provided, the source is cited instead.


‘Enlarged Brain Size, Autism, Epilepsy And Cancer Linked To Newly Found Gene Mutations’

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Charting Autism’s Neural Circuitry

Main Category: Autism
Also Included In: Genetics;  Clinical Trials / Drug Trials
Article Date: 05 Jul 2012 – 0:00 PDT Current ratings for:
Charting Autism’s Neural Circuitry
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Deleting a single gene in the cerebellum of mice can cause key autistic-like symptoms, researchers have found. They also discovered that rapamycin, a commonly used immunosuppressant drug, prevented these symptoms.

The deleted gene is associated with Tuberous Sclerosis Complex (TSC), a rare genetic condition. Since nearly 50 percent of all people with TSC develop autism, the researchers believe their findings will help us better understand the condition’s development.

“We are trying to find out if there are specific circuits in the brain that lead to autism-spectrum disorders in people with TSC,” said Mustafa Sahin, Harvard Medical School associate professor of neurology at Boston Children’s Hospital and senior author on the paper. “And knowing that deleting the genes associated with TSC in the cerebellum leads to autistic symptoms is a vital step in figuring out that circuitry.”

This is the first time researchers have identified a molecular component for the cerebellum’s role in autism. “What is so remarkable is that loss of this gene in a particular cell type in the cerebellum was sufficient to cause the autistic-like behaviors,” said Peter Tsai, HMS instructor of neurology and the first author of this particular study.

These findings were published online in Nature.

TSC is a genetic disease caused by mutations in either one of two genes, TSC1 and TSC2. Patients develop benign tumors in various organs in the body, including the brain, kidneys and heart, and often suffer from seizures, delayed development and behavioral problems.

Researchers have known that there was a link between TSC genes and autism, and have even identified the cerebellum as the key area where autism and related conditions develop.

Previous studies have shown that certain cells essential for cerebellar function called Purkinje cells, which are among the largest neurons in the human brain, are fewer in number in patients with autism. To better understand the relationship between Purkinje cells and autism, Sahin and his team deleted copies of the TSC1 gene in the Purkinje cells of mice. Some mice had only one copy of the gene deleted, while others had both of their copies deleted.

In both cases, deleting this gene caused the three main signs of autistic-like behaviors:

Abnormal social interactions. The mice spent less time with each other and more with inanimate objects, compared to controls.

Repetitive behaviors. The mice spent extended amounts of time pursuing one activity or with one particular object far more than normal.

Abnormal communication. Ultrasonic vocalizations, the communication method used among rodents, were highly distressed.

The researchers also tested learning. “These mice were able to learn new things normally,” said Tsai, “but they had trouble with ‘reversal learning,’ or re-learning what they had learned when their environment changed.”

Tsai and colleagues tested this by training the mice to swim a particular path in which a platform where they could rest was set up on one side of the pool. When the researchers moved the platform to the other side of the pool, the mice had greater difficulty than the control mice re-learning to swim to the other side.

“These changes in behavior indicate that the TSC1 gene in Purkinje cells, and by extension, the cerebellum, are a part of the circuitry for autism disorders,” emphasized Sahin.

The researchers also found that the drug rapamycin averted the effects of the deleted gene. Administering the drug to the mice during development prevented the formation of autistic-like behaviors.

Currently, Sahin is the sponsor-principal investigator for an ongoing Phase II clinical trial to test the efficacy of everolimus, a compound in the same family as rapamycin, in improving neurocognition in children with TSC. The trial will be open for enrollment until December 2013.

“Our next step will be to see how the abnormalities in Purkinje cells affect autism-like development. We don’t know how generalizable our current findings are, but understanding mechanisms beyond TSC genes might be useful to autism,” said Tsai.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our autism section for the latest news on this subject. This study was supported by the National Institutes of Health (R01 NS58956), the John Merck Scholars Fund, Autism Speaks, Nancy Lurie Marks Family Foundation, Children’s Hospital Boston Translational Research Program, the Children’s Hospital Boston Mental Retardation and Developmental Disabilities Research Center (P30 HD18655).
Sahin serves as a consultant and site primary investigator for Novartis.
Harvard Medical School Please use one of the following formats to cite this article in your essay, paper or report:

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Harvard Medical School. “Charting Autism’s Neural Circuitry.” Medical News Today. MediLexicon, Intl., 5 Jul. 2012. Web.
5 Jul. 2012. APA

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‘Charting Autism’s Neural Circuitry’

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New Gene Mutations Found That Lead To Enlarged Brain Size, Cancer, Autism, Epilepsy

Main Category: Neurology / Neuroscience
Also Included In: Genetics;  Cancer / Oncology;  Autism
Article Date: 03 Jul 2012 – 0:00 PDT Current ratings for:
New Gene Mutations Found That Lead To Enlarged Brain Size, Cancer, Autism, Epilepsy
4 stars1 star
A research team led by Seattle Children’s Research Institute has discovered new gene mutations associated with markedly enlarged brain size, or megalencephaly. Mutations in three genes, AKT3, PIK3R2 and PIK3CA, were also found to be associated with a constellation of disorders including cancer, hydrocephalus, epilepsy, autism, vascular anomalies and skin growth disorders. The study, “De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes,” was published online in Nature Genetics.

The discovery offers several important lessons and hope for the future in medicine. First, the research team discovered additional proof that the genetic make-up of a person is not completely determined at the moment of conception. Researchers previously recognized that genetic changes may occur after conception, but this was believed to be quite rare. Second, discovery of the genetic causes of these human diseases, including developmental disorders, may also lead directly to new possibilities for treatment.

AKT3, PIK3R2 and PIK3CA are present in all humans, but mutations in the genes are what lead to conditions including megalencephaly, cancer and other disorders. PIK3CA is a known cancer-related gene, and appears able to make cancer more aggressive. Scientists at Boston Children’s Hospital recently published similar findings related to PIK3CA and a rare condition known as CLOVES syndrome in the American Journal of Human Genetics.

Physician researcher James Olson, MD, PhD, a pediatric cancer expert at Seattle Children’s and Fred Hutchinson Cancer Research Center who was not affiliated with the study, acknowledged the two decades-worth of work that led to the findings. “This study represents ideal integration of clinical medicine and cutting-edge genomics,” he said. “I hope and believe that the research will establish a foundation for successfully using drugs that were originally developed to treat cancer in a way that helps normalize intellectual and physical development of affected children. The team ‘knocked it out of the park’ by deep sequencing exceptionally rare familial cases and unrelated cases to identify the culprit pathway.” The genes – AKT3, PIK3R2 and PIK3CA – all encode core components of the phosphatidylinositol-3-kinase (P13K)/AKT pathway, the “culprit pathway” referenced by Olson.

The research provides a first, critical step in solving the mystery behind chronic childhood conditions and diseases. At the bedside, children with these conditions could see new treatments in the next decade. “This is a huge finding that provides not only new insight for certain brain malformations, but also, and more importantly, provides clues for what to look for in less severe cases and in conditions that affect many children,” said William Dobyns, MD, a geneticist at Seattle Children’s Research Institute. “Kids with cancer, for example, do not have a brain malformation, but they may have subtle growth features that haven’t yet been identified. Physicians and researchers can now take an additional look at these genes in the search for underlying causes and answers.”

Researchers at Seattle Children’s Research Institute will now delve more deeply into the findings, with an aim to uncover even more about the potential medical implications for children. “Based on what we’ve found, we believe that we can eventually reduce the burden of and need for surgery for kids with hydrocephalus and change the way we treat other conditions, including cancer, autism and epilepsy,” said Jean-Baptiste Rivière, PhD, at Seattle Children’s Research Institute. “This research truly helps advance the concept of personalized medicine.”

Drs. Dobyns, Rivière and team made this discovery through exome sequencing, a strategy used to selectively sequence the coding regions of the genome as an inexpensive but effective alternative to whole genome sequencing. An exome is the most functionally relevant part of a genome, and is most likely to contribute to the phenotype, or observed traits and characteristics, of an organism.

Article adapted by Medical News Today from original press release. Click ‘references’ tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject. Background On Researchers:
Seattle Children’s Research Institute conducted this study in collaboration with teams from University of Washington Genome Sciences Department, FORGE (Finding of Rare Disease Genes) Canada Consortium, Cedars Sinai Medical Center and University of Sussex.
Dr. Dobyns, who is also a UW professor of pediatrics, is a renowned researcher whose life-long work has been to try to identify the causes of children’s developmental brain disorders such as megalencephaly. He discovered the first known chromosome abnormality associated with lissencephaly (Miller-Dieker syndrome) while still in training in child neurology at Texas Children’s Hospital in 1983. That research led, 10 years later, to the discovery by Dobyns and others of the first lissencephaly gene known as LIS1.
Dr. Rivière is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. As a lead researcher in the Dobyns lab, he also identified two new genes that cause Baraitser-Winter syndrome, a rare smooth brain malformation.
Co-authors on this study include: Jean-Baptiste Rivière, PhD, Banting Postdoctoral Fellow at Seattle Children’s Research Institute; Judith St-Onge, Seattle Children’s Research Institute; Christopher Sullivan, Seattle Children’s Research Institute; Thomas Ward, Seattle Children’s Research Institute; Ghayda Mirzaa, MD, University of Chicago; Brian O’Roak, PhD, University of Washington; Jay Shendure, MD, PhD, University of Washington; Mark O’Driscoll, PhD, University of Sussex; John Graham, MD, ScD, Cedars Sinai Medical Center; Kym Boycott, MD, PhD, University of Ottawa, Children’s Hospital of Eastern Ontario; and many other physicians and scientists from North America and Europe.
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‘New Gene Mutations Found That Lead To Enlarged Brain Size, Cancer, Autism, Epilepsy’

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