Corporate Banner
Satellite Banner
Next Gen Sequencing
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Cautionary Tale on Genome-Sequencing Diagnostics for Rare Diseases

Published: Tuesday, May 14, 2013
Last Updated: Tuesday, May 14, 2013
Bookmark and Share
Studies in several children have raising new questions about inheritance, genomic sequencing, and diagnostic.

Children born with rare, inherited conditions known as Congenital Disorders of Glycosylation, or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars. Properly diagnosing a child with CDG and pinpointing the exact sugar gene that's mutated can be a huge relief for parents—they better understand what they're dealing with and doctors can sometimes use that information to develop a therapeutic approach. Whole-exome sequencing, an abbreviated form of whole-genome sequencing, is increasingly used as a diagnostic for CDG.

But researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) recently discovered three children with CDG who are mosaics—only some cells in some tissues have the mutation. For that reason, standard exome sequencing initially missed their mutations, highlighting the technique's diagnostic limitations in some rare cases. These findings were published April 4 in the American Journal of Human Genetics.

"This study was one surprise after another," said Hudson Freeze, Ph.D., director of Sanford-Burnham's Genetic Disease Program and senior author of the study. "What we learned is that you have to be careful—you can't simply trust that you'll get all the answers from gene sequencing alone."

Searching for a rare disease mutation

Complicated arrangements of sugar molecules decorate almost every protein and cell in the body. These sugars are crucial for cellular growth, communication, and many other processes. As a result of a mutation in an enzyme that assembles these sugars, children with CDG experience a wide variety of symptoms, including intellectual disability, digestive problems, seizures, and low blood sugar.

To diagnose CDG, researchers will test the sugar arrangements on a common protein called transferrin. Increasingly, they'll also look for known CDG-related mutations by whole-exome sequencing, a technique that sequences only the small portion of the genome that encodes proteins. The patients are typically three to five years old.

A cautionary tale for genomic diagnostics

In this study, the researchers observed different proportions and representations of sugar arrangements depending on which tissues were examined. In other words, these children have the first demonstrated cases of CDG "mosaicism"—their mutations only appear in some cell types throughout the body, not all. As a result, the usual diagnostic tests, like whole-exome sequencing, missed the mutations. It was only when Freeze's team took a closer look, examining proteins by hand using biochemical methods, did they identify the CDG mutations in these three children.

The team then went back to the three original children and examined their transferrin again. Surprisingly, these readings, which had previously shown abnormalities, had become normal. Freeze and his team believe this is because mutated cells in the children's livers died and were replaced by normal cells over time.

"If the transferrin test hadn't been performed early on for these children, we never would've picked up these cases of CDG. We got lucky in this case, but it just shows that we can't rely on any one test by itself in isolation," Freeze said.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
How Did The Giraffe Get Its Long Neck?
Clues about the evolution of the giraffe’s long neck have now been revealed by new genome sequencing.
Big Data Can Save Lives
The sharing of genetic information from millions of cancer patients around the world could be key to revolutionising cancer prevention and care, according to a leading cancer expert from Queen's University Belfast.
Making Genetic Data Easier to Search
Scripps team streamlines biomedical research by making genetic data easier to search.
Collaborative Study of WES Offers New Hope
Company has announced that the collaborative study of whole exome sequencing offers new hope for children with white matter disorders.
Using Portable Nanopore DNA Sequencers to Combat Wildlife Crime
University of Leicester researchers aim to develop a test using DNA to identify species at crime scenes in as little as an hour.
TGAC Installs Largest SGI UV 300 Supercomputer for Life Sciences
The Genome Analysis Centre (TGAC) partners with Global HPC hardware giant SGI to address the most complex problems in genomics analysis.
Shining A Light On Bladder Cancer
Researchers scrutinize patterns of mutations in bladder tumor genomes, gleaning insights into the roles of DNA repair and tobacco-related DNA damage.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
Five New Breast Cancer Genes Found
Discovery of mutations paves the way for personalised treatment of breast cancer.
New Neurodevelopmental Syndrome Identified
Study pinpoints underlying genetic mutations, raising hopes for targeted therapies.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!