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!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences