MUHC and McGill scientists explain genetic disease first discovered in Quebec 24 years ago

Scientists at the MUHC and McGill University have identified a gene essential for the uptake of vitamin B12 in human cells. The discovery of this gene finally completes a 24 year-old hunt for the cause of an incredibly rare genetic disorder called, cblF combined homocystinuria and methylmalonic aciduria (cblF-Hcy-MMA), first documented in a Quebec infant in 1985. The work, which was funded in part by the CIHR and involved collaboration among researchers in Canada, Germany, Switzerland and France, was published online in Nature Genetics this week.

Two contrasting approaches combined to crack the genetic puzzle at the heart of cblF. In Germany, Dr. Frank Rutsch and his colleagues used DNA from patients to conduct a genome scan for shared regions of DNA sequence. Simultaneously in Montreal, Isabelle R. Miousse, a graduate student of Dr. David Rosenblatt – Chairman of Human Genetics and Director of the Division of Medical Genetics in Medicine at McGill – conducted research that confirmed a gene on chromosome 6 could correct the cellular defect in cells from these patients. Strikingly, the vast majority of patients with this rare disease share a common mutation despite the fact that they come from different countries and different ethnic groups.

"This discovery offers the prospect of earlier diagnosis and treatment options for this disease," says Dr. Rosenblatt, who was the first to describe this rare genetic condition in 1985. "Vitamin B12 plays an important role in our lives," says Dr. Rosenblatt. "Studying rare genetic diseases like cblF-Hcy-MMA offers a window into its basic properties and how it behaves in healthy cells."

The cblF idisease is a rare genetic disorder characterized by an inability to metabolize vitamin B12. Patients afflicted with this condition build up toxic levels of homocysteine and methylmalonic acid in their bodies. Vitamin B12, which is found in all animal products-including dairy, eggs, meat, poultry, and fish, is vital for the synthesis of red blood cells and the maintenance of the nervous system. It also helps control homocysteine levels in the human body, an excess of which is associated with an increased risk of heart disease, stroke and dementia.

The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec. For further details visit: www.muhc.ca/research.

McGill, Canada's leading university, has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 33,000 students. Since 2000, more than 800 professors have been recruited to McGill to share their energy, ideas and cutting-edge research. McGill attracts students from more than 160 countries around the world. Almost half of McGill students claim a first language other than English – including 6,000 francophones – with more than 6,200 international students making up almost 20 per cent of the student body.