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!
First line of defence against influenza further decoded
21.02.2018 | Helmholtz-Zentrum für Infektionsforschung
Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates
21.02.2018 | Institute of Science and Technology Austria
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Life Sciences
21.02.2018 | Power and Electrical Engineering
21.02.2018 | Trade Fair News