Featured Research

from universities, journals, and other organizations

New gene mutations that lead to enlarged brain size, cancer, autism, epilepsy identified

Date:
June 29, 2012
Source:
Seattle Children's
Summary:
Scientist have discovered new gene mutations associated with markedly enlarged brain size, or megalencephaly.

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 was published online June 24 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.


Story Source:

The above story is based on materials provided by Seattle Children's. Note: Materials may be edited for content and length.


Journal Reference:

  1. 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, Wendy S Meschino, James D Reggin, Anand K Saggar, Tally Lerman-Sagie, Gökhan Uyanik, Rosanna Weksberg, Birgit Zirn, Chandree L Beaulieu, Jacek Majewski, Dennis E Bulman, Mark O'Driscoll, Jay Shendure, John M Graham, Kym M Boycott, William B Dobyns. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nature Genetics, 2012; DOI: 10.1038/ng.2331

Cite This Page:

Seattle Children's. "New gene mutations that lead to enlarged brain size, cancer, autism, epilepsy identified." ScienceDaily. ScienceDaily, 29 June 2012. <www.sciencedaily.com/releases/2012/06/120629211856.htm>.
Seattle Children's. (2012, June 29). New gene mutations that lead to enlarged brain size, cancer, autism, epilepsy identified. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2012/06/120629211856.htm
Seattle Children's. "New gene mutations that lead to enlarged brain size, cancer, autism, epilepsy identified." ScienceDaily. www.sciencedaily.com/releases/2012/06/120629211856.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins