Featured Research

from universities, journals, and other organizations

Elusive platelet count and limb development gene discovered

Date:
February 26, 2012
Source:
Wellcome Trust Sanger Institute
Summary:
Researchers have identified an elusive gene responsible for Thrombocytopenia with Absent Radii (TAR), a rare inherited blood and skeletal disorder. As a result, this research is now being transformed into a medical test that allows prenatal diagnosis and genetic counseling in affected families.

Section of bone marrow showing the megakaryocytes (black arrows), the precursor cells that produce the blood platelets.
Credit: University of Cambridge

Researchers have identified an elusive gene responsible for Thrombocytopenia with Absent Radii (TAR), a rare inherited blood and skeletal disorder. As a result, this research is now being transformed into a medical test that allows prenatal diagnosis and genetic counselling in affected families.

Related Articles


The team used genetic sequencing to discover that TAR results from low levels of the protein called Y14. They found that the syndrome occurs by a unique inherited mechanism.

Platelets are the second most abundant cell in the blood. Their main task is to survey the blood vessel wall for damage and to plug and repair it where required. Some people are born with low numbers of platelets and these rare conditions are thought to be inherited. TAR syndrome combines the unique features of low platelet count and prominent bleeding, especially in infancy, and skeletal abnormalities affecting the upper limb ranging from absence of the radial bone in the forearm to virtually total absence of upper limb. The genetic basis of TAR syndrome has eluded researchers for 50 years.

"Without the use of modern genomics technologies, the discovery of this unexpected mechanism of disease inheritance would have been much more difficult," said Dr Cornelis Albers, from the Sanger Institute and the University of Cambridge. "To achieve our latest findings, we deciphered about 40 million letters of genetic code in five patients."

Many people with TAR were known to have a deletion in one copy of chromosome 1, but this was thought not to be the whole story because parents who carry the same deletion do not suffer from TAR: other variants had to be involved. The team sequenced the genomes of people affected by the disorder who also carried the deletion and discovered that the vast majority of them had one of two variants of a gene called RBM8A. They found that when the genetic deletion and one of the variants are co-inherited by a child, TAR results.

RBM8A controls the production of the protein Y14. They found that the combination of the genetic deletion of one copy of the RBM8A gene and the variants on the other copy greatly reduces the level of Y14. The team concluded that it is low levels of Y14 that affect platelet formation and cause TAR disorder.

"The lack of production of adequate amounts of the protein Y14 in TAR patients only seems to affect the formation of platelets but not of other blood cells." said Dr Cedric Ghevaert from the University of Cambridge. "We have shed some light on how some inherited disorders can present with such striking features associating seemingly unconnected characteristics such as skeletal and blood defects"

This is the first human disorder identified to be caused by a presumed defect of the Exon Junction Complex, part of the cellular machinery that contributes to producing messages that direct protein production. This study opens the path that could lead to the identification of the genetic basis of other similar inherited syndromes, which will help improvements in diagnosis, genetic counselling and patient care in the NHS and beyond.

"The discovery of the gene for TAR will make it simpler to diagnose more accurately future cases with a simple DNA test. This new test is currently being developed for the NHS as part of the international ThromboGenomics initiative led by Professor Ouwehand" commented Dr Ruth Newbury-Ecob, Honorary Reader in Medical Genetics and Consultant in Clinical Genetics at the University of Bristol Hospitals.


Story Source:

The above story is based on materials provided by Wellcome Trust Sanger Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Cornelis A Albers, Dirk S Paul, Harald Schulze, Kathleen Freson, Jonathan C Stephens, Peter A Smethurst, Jennifer D Jolley, Ana Cvejic, Myrto Kostadima, Paul Bertone, Martijn H Breuning, Najet Debili, Panos Deloukas, Rémi Favier, Janine Fiedler, Catherine M Hobbs, Ni Huang, Matthew E Hurles, Graham Kiddle, Ingrid Krapels, Paquita Nurden, Claudia A L Ruivenkamp, Jennifer G Sambrook, Kenneth Smith, Derek L Stemple, Gabriele Strauss, Chantal Thys, Chris van Geet, Ruth Newbury-Ecob, Willem H Ouwehand, Cedric Ghevaert. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nature Genetics, 2012; DOI: 10.1038/ng.1083

Cite This Page:

Wellcome Trust Sanger Institute. "Elusive platelet count and limb development gene discovered." ScienceDaily. ScienceDaily, 26 February 2012. <www.sciencedaily.com/releases/2012/02/120226153549.htm>.
Wellcome Trust Sanger Institute. (2012, February 26). Elusive platelet count and limb development gene discovered. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2012/02/120226153549.htm
Wellcome Trust Sanger Institute. "Elusive platelet count and limb development gene discovered." ScienceDaily. www.sciencedaily.com/releases/2012/02/120226153549.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
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