Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Single Gene Mutation Linked to Neurological Disorders

Published: Wednesday, October 16, 2013
Last Updated: Wednesday, October 16, 2013
Bookmark and Share
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.

A research team says a gene mutation that causes a rare but devastating neurological disorder known as Lesch-Nyhan syndrome appears to offer clues to the developmental and neuronal defects found in other, diverse neurological disorders like Alzheimer's, Parkinson's and Huntington's diseases.

The findings, published in the Oct.9 issue of the journal PLOS ONE, provide the first experimental picture of how gene expression errors impair the ability of stem cells to produce normal neurons, resulting instead in neurological disease. More broadly, they indicate that at least some distinctly different neurodevelopmental and neurodegenerative disorders share basic, causative defects.

The scientists say that understanding defects in Lesch-Nyhan could help identify errant processes in other, more common neurological disorders, perhaps pointing the way to new kinds of therapies.

Lesch-Nyhan syndrome is caused by defects in the HPRT1 gene (short for hypoxanthine guanine phosphoribosyltransferace, the enzyme it encodes), a gene that is well-known for its essential "housekeeping duties," among them helping generate purine nucleotides - the building blocks of DNA and RNA.

Mutations in the gene result in deficiencies in the HPRT enzyme, leading to defective expression of the neurotransmitter dopamine and subsequent abnormal neuron function. HPRT mutation is known to be the specific cause of Lesch-Nyhan, an inherited neurodevelopmental disorder characterized by uncontrollable repetitive body movements, cognitive defects and compulsive self-mutilating behaviors. The disorder was first described in 1964 by medical student Michael Lesch and his mentor, William Nyhan, MD, professor emeritus at UC San Diego School of Medicine.

Using mouse embryonic stem cells modified to be HPRT-deficient, Friedmann and colleagues discovered that the cells do not develop normally. Instead, they differentiate from full-fledged neurons into cells that resemble and partially function as neurons, but also perform functions more typical of glial cells, a kind of supporting cell in the central nervous system. In addition, they noted that HPRT deficiency causes abnormal regulation of many cellular functions controlling important operational and reproduction mechanisms, DNA replication and repair and many metabolic processes.

"We believe that the neural aberrations of HPRT deficiency are the consequence of these combined, multi-system metabolic errors," said Friedmann. "And since some of these aberrations are also found in other neurological disorders, we think they almost certainly play some role in causing the neurological abnormalities in diseases like Alzheimer's, Parkinson's, Huntington's and possibly others. That makes them potential therapeutic targets for conditions that currently have limited or no treatments, let alone cures."

The task now is to further parse and better understand the many pathways that cause abnormal brain and brain cell development, and how those pathways are also disturbed in other neurological disorders. Those defects will probably not affect HPRT directly, said Friedmann, but rather will correspond to some of the same metabolic and genetic errors that occur as a result of HPRT deficiency. Once those pathways are identified, they may become good targets for more effective forms of therapy.

Further Information
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 2,800+ scientific posters on ePosters
  • More Than 4,000+ 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 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.

Related Content

When it Comes to Breast Cancer, Common Pigeon is No Bird Brain
If pigeons went to medical school and specialized in pathology or radiology, they’d be pretty good at distinguishing digitized microscope slides and mammograms of normal vs. cancerous breast tissue, a new study has found.
Monday, November 30, 2015
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
Monday, November 23, 2015
Some 3-D Printed Objects Are Toxic
Researchers at the University of California, Riverside have found parts produced by some commercial 3-D printers are toxic to certain fish embryos.
Monday, November 09, 2015
Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 2015
Clearest Ever Images of Enzyme that Plays Key Roles in Aging, Cancer
UCLA-led research on telomerase could lead to new strategies for treating disease
Monday, October 19, 2015
Crop Cure
Scientists in new center to use medical research techniques to help food crops withstand drought and climate change.
Friday, October 16, 2015
Rare Childhood Leukemia Reveals Surprising Genetic Secrets
A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.
Thursday, October 15, 2015
Sustaining Our Salad
Improving lettuce crops is the aim of a new, $4.5 million grant, awarded to University of California, Davis, researchers by the U.S. Department of Agriculture's National Institute of Food and Agriculture.
Thursday, October 15, 2015
Double Enzyme Hit May Explain Common Cancer Drug Side Effect
Mouse study suggests genomic screening before treatment may help prevent anemia.
Wednesday, October 14, 2015
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
Wednesday, September 30, 2015
Influenza A Viruses More Likely To Emerge In East Asia Than North America
Novel strains of influenza A are more likely to emerge in East Asia than in North America, according to a global analysis by the One Health Institute at the UC Davis School of Veterinary Medicine and EcoHealth Alliance.
Wednesday, September 30, 2015
Opening the Door to Safer, More Precise Cancer Therapies
New method regulates when, and how strongly, cancer-killing therapeutic T cells are activated.
Tuesday, September 29, 2015
Crunching Numbers to Combat Cancer
UCSF receives $5 million to integrate data from cancer research models.
Wednesday, September 16, 2015
Virus In Cattle Linked To Human Breast Cancer
A new study by UC Berkeley researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer.
Wednesday, September 16, 2015
Ultrafast DNA Diagnostics
New technology developed by UC Berkeley bioengineers promises to make a workhorse lab tool cheaper, more portable and many times faster by accelerating the heating and cooling of genetic samples with the switch of a light.
Monday, August 03, 2015
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Promising Drug Combination for Advanced Prostate Cancer
A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.
A Cellular Symphony Responsible for Autoimmune Disease
Broad Institute researchers have used a novel approach to increase our understanding of the immune system as a whole.
When it Comes to Breast Cancer, Common Pigeon is No Bird Brain
If pigeons went to medical school and specialized in pathology or radiology, they’d be pretty good at distinguishing digitized microscope slides and mammograms of normal vs. cancerous breast tissue, a new study has found.
Editing of LIMS Data Made Faster and More Efficient in Matrix Gemini
The latest version of the Matrix Gemini LIMS (Laboratory Information Management System) from Autoscribe Informatics now provides faster and more efficient editing of LIMS data by eliminating the need for a second editing screen.
University of Edinburgh, Selcia Achieve Key Milestones in Drug Development Program
Scientists from the University of Edinburgh, working with Selcia, have successfully passed the 20-month milestone targets of a 30-month Wellcome Trust SDDi £2.5 million project to design novel treatments for sleeping sickness.
Red Clover Genome to Help Restore Sustainable Farming
The Genome Analysis Centre (TGAC) in collaboration with IBERS, has sequenced and assembled the DNA of red clover to help breeders improve the beneficial traits of this important forage crop.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos