From family to gene: A 20 year pathway


Since first identifying a rare and lethal genetic disease in Quebec more than 20 years ago, scientists at the Montreal Neurological Institute (MNI), McGill University in collaboration with colleagues world-wide have worked hard to advance knowledge and understanding of Action myoclonus-renal failure syndrome (AMRF), a disorder affecting the brain and kidneys. In 1986, wife and husband team, Eva and Frederick Andermann published a study clinically characterizing AMRF based on their work with a few Quebec patients and their families. Dr. Frederick Andermann, neurologist and epileptologist is renowned for his exceptional diagnostic skills and ability to recognize new neurological syndromes. Dr. Eva Andermann, a neurogeneticist, works to identify the genetic basis of neurological disorders, studying the families in Quebec and Europe, and collaborating with molecular geneticists and other researchers worldwide. In 2004, they published a larger study with cases identified around the world, including Cuba, Italy, Germany, Australia and the US. In the latest study, published recently in The American Journal of Human Genetics, the global team was led by collaborators Dr. Samuel Berkovic and Dr. John Mulley in Australia who used cutting-edge molecular biological techniques and developed a new strategy to identify the gene, specifically SCARB2/LIMP-2, involved in AMRF. The development of this novel molecular strategy paves the way for the discovery of genes responsible for other rare autosomal recessive diseases

Progress in investigating rare and lethal diseases is often difficult due to the extremely limited number of affected individuals. Such diseases are often overlooked or misdiagnosed. This is particularly true for AMRF which was often misinterpreted as a pure renal condition. This study by Berkovic and colleagues is one of the first to successfully identify the genetic mutation in this type of rare disease by using novel molecular methods in single patients. These findings will allow for genetic screening and counseling in AMRF, new diagnostic tests, and more effective therapeutic strategies. Significantly, it also allows for improved quality of life and hope for affected families, as well as addressing an important public health issue for Quebec and other regions around the world.

“I am thrilled and motivated that there has been such remarkable progress in the past 20 years since we identified AMRF. The discovery of the gene provides a light at the end of the tunnel for our patients and their families – giving them hope” says Dr. Eva Andermann, Director of the Neurogenetics Unit at the MNI, who first presented the disease at an international scientific conference in 1984. Dr. Andermann has spent much of her career working with her husband to identify and describe rare genetic diseases, such as Joubert syndrome and Andermann syndrome or familial agenesis of the corpus callosum with sensorimotor neuropathy. The Andermanns have also identified and provided much of the groundwork leading to the discovery of the genetic basis of such disorders as Unverricht-Lundborg disease, Lafora disease, both chorea-acanthocytosis and Tay-Sachs disease in French-Canadians, juvenile Tay-Sachs disease in Lebanese Canadians, Canavan disease in the French-Canadian and First Nation populations, neuronal ceroid lipofuscinoses in Newfoundlanders as well as many different forms of epilepsy and malformations of brain development.

Discovering the genetic basis of rare recessive disorders has in part been facilitated by the recognition of the founder effect, in which a population originating from a small group of settlers has low levels of genetic variation. For example, 2,600 individuals migrated from France to Quebec between 1608 and 1760, and experienced a genetic bottleneck, creating a population with high incidence of rare genetic diseases due to limited gene pools. Recognizing this, the Quebec government is planning to launch a pilot project for population screening of autosomal recessive diseases that have a particularly high prevalence in the Saguenay Lac St-Jean region of Quebec. Dr. Anne Andermann, daughter of the Andermanns, who specializes in public health, acted as a consultant on this project.

The AMRF study was supported by the National Health and Medical Research Council of Australia, The Canadian Institutes of Health Research (CIHR), the Savoy Foundation, the Thyne Reid Charitable Trusts, and the Deutsche Forschungsgemeinschaft.

On October 23rd to 25th, the achievements of Frederick and Eva Andermann will be honored and celebrated at a symposium, organized by Professors Jean Gotman, Francois Dubeau and David Colman, Director of the MNI, entitled: Epilepsy at the Cutting Edge. More than 40 invited scientists and physicians from around the world, many of whom are collaborators and former MNI trainees, will speak on a wide range of topics in the field and reflect on the Andermanns’ significant contributions. The keynote speaker is Dr. Samuel Berkovic,and main topics of the symposium include: malfomations of cortical development, generalized and focal epilepsies, as well as surgical treatment of epilepsy. Some former trainees will also deliver personal recollections of their experiences at the MNI.

The Andermanns have received many honours and awards during their careers. Frederick Andermann received the Wilder Penfield Prize of the Prix du Québec, and is an Officer of the Order of Canada. He is also Vice-President of the International League Against Epilepsy. Eva Andermann is an Ambassador of the International League Against Epilepsy, and honorary member of the German, Brazilian, Spanish and Polish Leagues Against Epilepsy. She recently received the Maude Abbott Life Achievement Award. The Andermanns received two awards jointly: the Governor General’s Medal for the 125th Anniversary of the Canadian Confederation and the Peter Emil Becker Prize of the joint Swiss, German and Austrian Societies for Neuropediatrics.

About the MNI

October 2009 marks the 75th anniversary of the MNI. The MNI is a McGill University research and teaching institute, dedicated to the study of the nervous system and neurological diseases. Founded in 1934 by the renowned Dr. Wilder Penfield, the MNI is one of the world's largest institutes of its kind. MNI 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 MNI, with its clinical partner, the Montreal Neurological Hospital (MNH), part of the McGill University Health Centre, continues to integrate research, patient care and training, and is recognized as one of the premier neuroscience centres in the world. At the MNI, we believe in investing in the faculty, staff and students who conduct outstanding research, provide advanced, compassionate care of patients and who pave the way for the next generation of medical advances. Highly talented, motivated people are the engine that drives research - the key to progress in medical care. A new building, the North Wing Expansion, is currently under construction and will house state-of-the-art brain imaging facilities. Once the construction is completed and the new building is fully equipped, the scientific community focused on brain imaging research at the MNI will be without equivalent anywhere in the world.

Contact Information

Anita Kar
Montreal Neurological Institute
anita.kar [at]
Office Phone: 
(514) 398-3376