Navigation Links
A cautionary tale on genome-sequencing diagnostics for rare diseases
Date:5/9/2013

LA JOLLA, Calif., May 10, 2013 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 parentsthey 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 mosaicsonly 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 carefulyou 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.


'/>"/>

Contact: Patrick Bartosch
pbartosch@sanfordburnham.org
407-745-2097
Sanford-Burnham Medical Research Institute
Source:Eurekalert

Related medicine news :

1. Supplements and cancer prevention: A cautionary tale
2. BIDMC and Diagnostics For All create first low-cost, paper-based, point of care liver function test
3. Canada In Vitro Diagnostics Market Analysis and Forecasts to 2017 in New Research Report at RnRMarketResearch.com
4. Mayo Clinic and SV Bio enter strategic relationship on genome diagnostics and interpretation
5. Diagnostic Marketing Association Names Siemens Healthcare Diagnostics its 2012 Marketer of the Year
6. Advanced Mold Diagnostics Receives Angie's List Super Service Award for 4th Straight Year
7. ORNLs awake imaging device moves diagnostics field forward
8. Penn Medicines new center for personalized diagnostics unlocks cancers secrets
9. Expert Panel to Discuss Perspectives on Evaluating Novel Diagnostics for Reimbursement at 2013 Next Generation Dx Summit In Washington, DC
10. AstraZeneca and DNDi to collaborate on drug screening for neglected tropical diseases
11. Range of diagnostic spinal fluid tests needed to differentiate concurrent brain diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/30/2016)... , ... April 30, 2016 , ... “Aging well is a challenge for all of us, but there are things ... Parul T. Kohli . “Research is showing more and more that there are simple, yet ... and disability as we age.” Top priorities Dr. Kohli’s recommends for her patients include;, ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... Footwear Foundation, the national charitable foundation serving the footwear industry, has broken all ... representing more than 130 companies across 23 states during the months of April ...
(Date:4/29/2016)... (PRWEB) , ... April 29, 2016 , ... ... the heart of our nation’s productivity, stability, even security. Most importantly, employees are ... organizations. , Then why are American workers so unhappy? , Just under half ...
(Date:4/29/2016)... Fla. (PRWEB) , ... April 29, 2016 , ... ... Hospital surgeon reveals that infants born with severe congenital diaphragmatic hernia have better ... is born with congenital diaphragmatic hernia (CDH)—a condition where the diaphragm fails to ...
(Date:4/29/2016)... ... 29, 2016 , ... The Gluten-Free Certification Program (GFCP), in ... the launch of the GFCP Scoop in response to consumer demand ... the GFCP Scoop site is to keep the gluten-free community updated ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... Italy , April 27, 2016 ... linear accelerator (MR-linac) platform will be the focal point ... meeting of the European Society for Radiotherapy & Oncology, ... Elekta,s MR-linac integrates a state-of-the-art radiotherapy system and a ... physician to clearly see the patient,s anatomy in real ...
(Date:4/27/2016)... Shire plc (LSE: SHP, NASDAQ: ... Financial Officer, will present at the Deutsche Bank 41st Annual ... on Wednesday, May 04, 2016, 10:00 am EDT (15:00 BST). ... the Presentations and Webcasts section of Shire,s Investor website at ... be available on this same website for approximately 90 days. ...
(Date:4/27/2016)... April 27, 2016 At the ... launch of a Phase 2 clinical study of its ... patients undergoing cochlear implantation (CI) surgery. This large, placebo-controlled, ... Germany and France ... ear at the time of surgery. "Despite advances in ...
Breaking Medicine Technology: