Isabelle Thiffault (PhD student)
Grant holder 2003-2005

This short article has been subjected to different little steps which I have taken in the course of the last five years of training in genetics. It gives me great pleasure to share with you my progress on the subject which you are examining, ataxia, and to take advantage of this opportunity to thank you for offering me a student bursary for the year 2004-2005.

I completed my Bachelor’s degree in medical biology at the Université du Québec de Trois-Rivières in April 2001. In January 2001 I undertook a training period in molecular diagnosis in hereditary cancers in the laboratory at the Jewish General Hospital of Montreal. Since this time, I realized the importance of the implication of genetics in current medicine. I acquired more than a year of experience as a research assistant in the different centres affiliated with McGill in colon, prostate, and breast cancer and the infantile syndrome of Proteus. The collection of my research led to 7 publications, of which there were three primary authors as well as two articles going to press. I obtained my Master’s degree officially at McGill University in May 2004.

Presentation of the research project

In July 2003, I happily met Dr. Bernard Brais. The main reason which motivated my laboratory choice was the research project on this new form of recessive ataxia more frequent in the French-Canadian population. This project presented different challenges but was complementary to my previous research projects on the characterization of the founding effects in colon cancer and prostate cancer in diverse populations. My doctoral project will permit me to familiarize myself with all the steps of positional cloning and to acquire a mastery of several techniques of molecular and protoemetabolic biology. Furthermore, the direct link between fundamental and clinical research are inherent in this project, and ensure the evident multidisciplinary repercussions of the projects.

Recessive ataxias are a heterogenous group of neurodegenerative hereditary diseases. Three forms of hereditary recessive ataxias have been described in the French-Canadian population, Friedreich’s ataxia, the recessive spastic ataxia of Charlevoix Saguenay, and the ataxia with oculomotor apraxia (AOA2). In the present research, we have carried out the recruitment of patients, the clinical revision of the files of spastic ataxia as well as the research of genealogical information on the families.

Description of the cohort and of the clinical phenotype

We recruited 19 families of whom 25 afflicted patients presented a new ataxic phenotype. More than 50% of our families are originally from Portneuf or have a genealogical link with the region. The phenotype consists in the development of an ataxia between the ages of 3 and 20 years old, accompanied by dysarthria and spasticity. There is a great interfamilial and intrafamilial phenotypic variability. In the most serious cases, we observed the presence of scoliosis, dystonia, mild intellectual retardation, cortical atrophy and the presence of leukodystrophy. There is no clinical description of similar cases in the literature. A screening of the entire human genome with the help of the DNA of the patients permitted us to establish that a region of the genome common to all the families must contain the mutated gene responsible for this form of ataxia. Genetic analyses suggest the presence of more than three mutations in Quebec. The most common of the mutations would be shared by 75% of the carriers. This project has as its principal goal to identify the gene and the mutations responsible for this new form of French-Canadian recessive ataxia associated with the region of Portneuf. As soon as this step is completed, we will be able to offer a diagnostic test, offer services of genetic counselling for this disease in Quebec, most particularly in the region of Portneuf, and study the functioning and the protein of this gene. This project will also lead to a greater understanding of the physiopathology of ataxias.

See the research on Portneuf Ataxia in Brain magasine of may 2006