Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
New study first to identify cause of rare genetic metabolic disorder

New study first to identify cause of rare genetic metabolic disorder

gene
Credit: CC0 Public Domain

A new study from BC Children’s Hospital, the University of British Columbia (UBC) and an international team of researchers published in the New England Journal of Medicine is the first to identify a rarely-seen type of DNA mutation as the cause of an inherited metabolic disorder.

Inherited metabolic disorders—where the body can’t break down specific nutrients from food leading to a range of serious health problems—are often caused by a defective gene.

In this important study, researchers found an unusual genetic mutation behind three children’s undiagnosed, degenerative conditions: a repeat expansion of DNA. In this specific mutation, the gene appears undamaged but does not function because the DNA adjacent to it has extended several hundred times its normal length.

“To detect this kind of DNA multiplication, you can only use whole genome sequencing and have to search through billions of pieces of DNA; it’s truly a search for the needle in the haystack,” said lead author Dr. Clara van Karnebeek. “With our new approach we have finally solved our mystery cases, and we now expect to find the genetic cause of other, as of yet unexplained, genetic metabolic diseases.”

To date, DNA repeat expansions have been linked to approximately 30 different diseases.

“For kids with rare diseases and their families, finding the root causes of their disorders is tremendously important,” said Dr. Wyeth Wasserman, a co-author of the study. “A diagnosis gives us the potential to intervene, relieves undeserved parental guilt, and provides insights into more common diseases.”

For a child with an unexplained medical condition, a diagnosis lays the groundwork for further research that could lead to new interventions such as gene therapy aimed at “turning on” the impaired gene, dietary modification or supplements that provide the nutrients the body is missing. Effective treatment can slow or stop damaging symptoms, improving the quality of life of children with rare disorders and their families.

In this study, initial work by van Karnebeek and her research team narrowed the search for the genetic causes of this rare disorder to key areas of the genome. However, after further investigations using exome sequencing and whole genome sequencing, the international research team couldn’t pinpoint the error in the DNA.

It’s here that researchers at BC Children’s took a novel approach. Through in-depth, manual analysis and the use of emerging bioinformatics tools and techniques study co-authors Dr. Britt Dr.ögemöller and Phillip Richmond discovered and confirmed that the gene responsible for the disorder was intact but a repeat expansion error prevented it from functioning.

“In our search, we focused on variations that would have been hard to discover through exome sequencing” said Dr.ögemöller. “After months of experimenting with various different analyses, we finally uncovered this novel genetic variant by using new targeted approaches aimed at identifying DNA repeat expansions.”

“These findings were made possible by a multidisciplinary approach and advances in technology, techniques and software,” said Richmond. “It wouldn’t have been possible as recently as two years ago and, most importantly, it shows us what to look for in other undiagnosed cases.”

The gene identified as the cause of this particular disorder is an enzyme that enables the body to turn an amino acid called glutamine into glutamate. More work is needed to determine how exactly this genetic error leads to disease, but it’s likely that either a build-up of glutamine or the lack of glutamate caused the children’s serious developmental delays and disabilities including difficulty with language, speech, balance and coordination.

Through collaborations with sequencing consortiums around the world, researchers were able to confirm that this particular repeat expansion was found in only 1 in 8,000 people, establishing the mutation as very rare.

Over one million Canadians suffer from a rare disease and in over 50 per cent of these cases, the underlying genetic cause of the illness remains unknown.

“We can do better for children with rare diseases. For the 50 per cent who can’t find answers, this discovery and new approach will help us dig in and potentially find the causes of their disease,” said Richmond.


International team of scientists detect cause of rare pediatric brain disorder


More information:
André B.P. van Kuilenburg et al, Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS, New England Journal of Medicine (2019). DOI: 10.1056/NEJMoa1806627

Provided by
University of British Columbia

Citation:
New study first to identify cause of rare genetic metabolic disorder (2019, April 15)
retrieved 28 April 2019
from https://medicalxpress.com/news/2019-04-rare-genetic-metabolic-disorder.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles