Featured Research

from universities, journals, and other organizations

Severe scoliosis linked to rare mutations

Date:
June 13, 2014
Source:
Washington University School of Medicine
Summary:
Children with rare mutations in two genes are about four times more likely to develop severe scoliosis than their peers with normal versions of the genes, scientists have found. One to 3 percent of the general population has some mild curvature of the spine. In about one in 10,000 children, scoliosis will produce curvature so pronounced that it requires corrective surgery.

Children with rare mutations in two genes are about four times more likely to develop severe scoliosis than their peers with normal versions of the genes, researchers have learned.
Credit: Matthew Dobbs

Children with rare mutations in two genes are about four times more likely to develop severe scoliosis than their peers with normal versions of the genes, scientists have found. The research at Washington University School of Medicine in St. Louis has identified genetic risk factors that predispose children to develop s-shaped curves in their spines that are dramatic enough to require surgery.

Related Articles


"We've had a difficult time finding ways to predict who will develop severe scoliosis, and these newly identified mutations have the potential to be very helpful," said senior author Christina A. Gurnett, MD, PhD.

The findings appear online in Human Molecular Genetics.

Drugs currently in clinical trials block a major growth pathway that these mutated genes, fibrillin-1 and fibrillin-2, control. If the same pathway is involved in scoliosis, doctors might be able to use these drugs to prevent scoliosis in some children with these mutations.

One to 3 percent of the general population has some mild curvature of the spine. In about one in 10,000 children, scoliosis will produce curvature so pronounced that it requires corrective surgery.

"These children often don't have any curvature of the spine early in adolescence, but then they go through a growth spurt, and that's when the curve appears," said Gurnett, associate professor of neurology. "Others have tried to predict severe disease using gender, age of onset and type of spine curve but haven't been very successful."

In 91 patients with acute scoliosis, the scientists sequenced the portions of the patients' DNA that encode proteins.

The most consistently mutated gene in the group was fibrillin-1, which makes a protein important to the tissues that connect many components of the body. A related gene, fibrillin-2, also often was mutated.

Additional sequencing of those genes in 852 patients with scoliosis and 669 subjects with healthy spines revealed that patients with specific mutations in both fibrillin-1 and fibrillin-2 had four times the risk of severe scoliosis than people without the genetic errors. The researchers used a new cost-effective method they developed that reduced the cost of sequencing each patient's genes to about $30 from $3,000-4,000.

To date, scientists have identified more than 600 mutations in fibrillin-1. Among the most serious are the mutations that produce Marfan syndrome, a condition that can cause the long bones of the body to overgrow and can weaken the body's connective tissue.

"Some variants of this important gene are associated with unusual tallness," Gurnett said. "There appears to be a spectrum of effects caused by changes in the gene, from simple alterations in height to severe scoliosis to more life-threatening conditions such as Marfan syndrome."

Clinical trials are underway in patients with Marfan syndrome to see whether drugs that block TGF-beta, a growth pathway controlled by fibrillin-1, can help treat the disorder. Gurnett and her colleagues are watching to see if the drugs affect growth of the spine. If they do, researchers may investigate using them to prevent scoliosis.

The researchers continue to look for additional genetic risk factors.

"We're very confident that genetic studies are going to open up new avenues for diagnosis and treatment of scoliosis," said coauthor Matthew Dobbs, MD, professor of orthopaedic surgery, who treats patients at St. Louis Children's Hospital and Shriners Hospital.

"We want to create a genetic testing panel that we can use to more accurately predict who will need treatment," Gurnett said. "If we can develop effective treatments and apply them early enough, we might one day be able to prevent the need for surgeries."


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Michael C. Purdy. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. G. Buchan, D. M. Alvarado, G. E. Haller, C. Cruchaga, M. B. Harms, T. Zhang, M. C. Willing, D. K. Grange, A. C. Braverman, N. H. Miller, J. A. Morcuende, N. L.-S. Tang, T.-P. Lam, B. K.-W. Ng, J. C.-Y. Cheng, M. B. Dobbs, C. A. Gurnett. Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Human Molecular Genetics, 2014; DOI: 10.1093/hmg/ddu224

Cite This Page:

Washington University School of Medicine. "Severe scoliosis linked to rare mutations." ScienceDaily. ScienceDaily, 13 June 2014. <www.sciencedaily.com/releases/2014/06/140613101705.htm>.
Washington University School of Medicine. (2014, June 13). Severe scoliosis linked to rare mutations. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2014/06/140613101705.htm
Washington University School of Medicine. "Severe scoliosis linked to rare mutations." ScienceDaily. www.sciencedaily.com/releases/2014/06/140613101705.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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