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:6/20/2017)... ... June 20, 2017 , ... In his newly appointed role ... May, Ph.D., recently accepted the distinguished Sun Corridor Export Award for his company’s ... (WNB), and 16 other businesses from Pima, Pinal, and Maricopa counties in Arizona, ...
(Date:6/20/2017)... West Hempstead, NY (PRWEB) , ... June 20, ... ... most experienced in the security systems industry has been selected as the partner ... , Amtrak is a passenger railroad service that provides medium- and long-distance intercity ...
(Date:6/20/2017)... ... 2017 , ... John D'Eri, CEO of Rising Tide Car Wash , ... during the Autism Society of America 's 49th annual conference to be ... Foundation (DJFF) was founded in 2002 as the nation's first autism organization focused ...
(Date:6/20/2017)... ... June 20, 2017 , ... MEDI+SIGN, ... like to officially welcome Anthony Stanowski, DHA, FACHE to the MEDI+SIGN Advisory Board. ... and expertise in healthcare will provide invaluable direction for the company,” says Andrew ...
(Date:6/20/2017)... ... , ... The law firm of Momkus McCluskey Roberts LLC congratulates ... DuPage County Bar Association’s Board of Directors. Cassioppi officially took on the leadership role ... Oak Brook. Momkus McCluskey Roberts LLC attorney Stacey A. McCullough was also installed as ...
Breaking Medicine News(10 mins):
(Date:6/1/2017)... , June 1, 2017 Nutriceutical Holdings (NH), ... Recommended Solutions (VRS), and KD Pharma Group have decided ... Holdings by KD Pharma Group. KD Pharma Group will ... option to acquire the entire company. "We ... They are committed to growing the NH companies by ...
(Date:5/26/2017)... -- Endo International plc (NASDAQ: ENDP ) announced today ... the Company in a fireside chat at Goldman Sachs, 38 ... 2017 at 10:40 a.m. PT / 1:40 p.m. ET. The ... Rancho Palos Verdes, CA. A live ... on the Company,s website at http://www.endo.com/investors/overview . Participants should ...
(Date:5/22/2017)... 22, 2017  As the specialty pharmacy industry ... to make the revolutionary shift from volume-based to ... ensuring positive patient outcomes and shaping the future ... focus away from clinical trials and toward data ... specialty drug therapy utilization in precise patient populations. ...
Breaking Medicine Technology: