Mutations in this gene were identified in individuals from around the world but one mutation occurs more frequently in French-Canadian patients from Quebec.
Published in the September issue of the American Journal of Human Genetics and selected for the Editors' Corner of the journal, the findings are crucial to the development of diagnostic tests and genetic counseling for families, and provide insights into a new mechanism for these disorders of the brain.
Currently, there are no cures for leukodystrophies which are a group of inherited neurodegenerative disorders affecting preferentially the white matter of the brain. White matter serves to cover nerve cell projections called axons, allowing nerve impulses to be correctly transmitted. Many children with a leukodystrophy appear normal at birth with very little or no indication that they have the disorder. Symptoms such as walking difficulties, falls or tremor gradually appear.
As they grow older they lose mobility, speech and develop swallowing difficulties, and as teenagers are often wheelchair bound or bed ridden. The majority of patients die prematurely. The evolution and symptoms vary according to the specific type of leukodystrophy. It is estimated that at least 30-40% of individuals with a leukodystrophy remain without a precise diagnosis despite extensive investigations.
The study identified the first mutations in the POLR3A gene in families from Quebec. Mutations in the same gene were found in patients from the USA, Syria, Guatemala, France, and other European countries. The international team was led by Drs Bernard Brais and Geneviève Bernard and included scientists from Montreal, Washington D.C., Dallas, Beirut, Paris, Clermont-Ferrand, and Bordeaux. The group was able to demonstrate that mutations in the same POLR3A gene localized on chromosome 10 were responsible for three clinically different forms of leukodystrophies: Tremor-Ataxia with Central Hypomyelination (TACH) first described in Quebec cases, Leukodystrophy with Oligodontia (LO), and 4H syndrome or Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism syndrome.
“We identified many different mutations in the POLR3A gene which codes for a key subunit of RNA Polymerase III (Pol III), a highly conserved protein complex with a crucial role in gene expression, and many other important pathways,” explains Dr. Brais. “This finding is surprising considering the fundamental role of Pol III. It is also an encouraging discovery because if we can identify which targets of Pol III, when decreased, lead to the disease, we could develop therapeutic strategies to replace them.” The research was conducted in the laboratory of Dr Brais at the Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM). Dr. Brais is now a clinician-scientist at The Montreal Neurological Institute and Hospital, The Neuro at McGill University, and Dr. Geneviève Bernard has recently been recruited as a clinician-researcher at The Montreal Children’s Hospital, McGill University Health Centre.
This research was funded by the Fondation sur les Leucodystrophies, created by a Quebec couple whose child is affected, in order to find a cure for this orphan disease (www.leucofondation.com). Support was also provided by l’Association Européenne contre les Leucodystrophies (http://www.ela-asso.com). The shared mission of both foundations is to increase public awareness of the disease, raise much needed funds for research and provide families with help and support. Support was also provided by the Réseau de médicine génétique appliquée du Québec (RMGA) and by the Fonds de recherche en santé du Québec (FRSQ).
The Montreal Neurological Institute and Hospital:
The Montreal Neurological Institute and Hospital — The Neuro, is a unique academic medical centre dedicated to neuroscience. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. The Montreal Neurological Institute was named as one of the Seven Centres of Excellence in Budget 2007, which provided the MNI with $15 million in funding to support its research and commercialization activities related to neurological disease and neuroscience.
Anita Kar | EurekAlert!
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering