Another Medical Cold Case Cracked by the MUHC鈥檚 鈥楧r. House鈥�
A team from the Research Institute of the 捆绑SM社区 Health Centre (RI-MUHC) led by Dr. Donald Vinh, the RI鈥檚 so-called 鈥淒r. House鈥� because of his research into rare diseases, has discovered a new human disease and the gene responsible for it, paving the way for the proper diagnosis of patients globally and the development of new therapies. Their findings are published in the Journal of Experimental Medicine.
Dr. Vinh has coined this new disease 鈥榗ombined immunoficiency鈥� or 鈥楥ID,鈥� and the gene responsible for it 鈥業COSLG鈥�. The disease is characterized by a weakened immune system and, because the body's ability to fight off infections is crippled, patients are susceptible to recurrent life-threatening infections such as pneumonias and debilitating infections, such as progressive warts.
New disease that affects the immune system
鈥淭his discovery will help patients who have escaped diagnosis - to now - be correctly diagnosed. By doing so, patients could benefit from aggressive monitoring of potential complications and earlier implementation of tailored therapies,鈥� explains Dr. Vinh, a researcher from the Infectious Diseases and Immunity in Global Health Program of the RI-MUHC and an associate professor in the Division of Infectious Diseases at 捆绑SM社区.
鈥淧inpointing this gene, will also help scientists identify who else in the family is at risk, including newborn babies before they become sick.鈥�
Gene with a link to Chromosome 21
The scientist says the knock-on from this discovery is the glimpse into whether it causes the immune deficiency reported in Down syndrome, which occurs as these individuals get older.
鈥淭his gene is on Chromosome 21 and it turns out that Down syndrome鈥檚 patients, who have three Chromosomes of 21 (instead of the usual two), have a similar problem with their immune system. We鈥檙e looking to see if this causes the immune deficiency reported in adults with Down鈥檚 syndrome,鈥� says Dr. Vinh, whose study of genetic defects of the immune system has fueled his "medical detective" reputation.
A patient with similar symptoms to the 鈥淏ubble Boy鈥�
Dr. Vinh鈥檚 discovery originated with the medical investigation of a 36-year-old male patient who had endured recurrent sinusitis and pneumonias, yeast infections and viral infections since childhood. Researchers used a state-of-the-art technique called 鈥榃hole Exome Sequencing鈥� inside Dr. Vinh鈥檚 laboratory to evaluate the patient鈥檚 genes and perform sophisticated analysis of his genes compared to that of his family members, to identify the abnormal gene that was responsible for his disease.
鈥淎t the clinical level, previous evaluations did not look at all his symptoms in their entirety as one disease but as individual and unrelated problems. But once you start putting the abnormalities together, you see our patient鈥檚 case was similar to that of the 鈥淏ubble Boy,鈥� which was the most severe form. Our patient鈥檚 disease is in the same family of conditions but because he was an adult, nobody thought to explore this possibility,鈥� says Dr. Vinh, who explains the 鈥淏ubble Boy鈥� name was given to a young child in the Seventies who was forced to live in a sterile bubble from birth due to his severely weakened immune system.
鈥淥nce we related our patient to the Bubble Boy鈥檚 disease, which we know is genetic, we discovered this new gene,鈥� says Dr. Vinh, who collaborated with Dr. Andr茅 Veillette, the Director of the IRCM Molecular Oncology Research Unit at the Montreal Clinical Research Institute (IRCM) in the study.
鈥淲e are so relieved to finally receive a diagnosis, after so many years of doctors not knowing what was wrong with me, and with the research providing the potential for eventual treatment for me. And knowing that our children are not affected is a major comfort,鈥� says the French-Canadian patient, who resides in Eastern Qu茅bec with his wife and two young children.
Dr. Vinh has already received numerous requests from physicians around the world to test patients who may have the same medical condition diagnosed in his own patient, providing hope for both patients and their families.
About the study
鈥楲oss of human ICOSL results in combined immunodeficiency鈥� was written by Lucie Roussel, Marija Landekic, Makan Golizeh, Christina Gavino, Ming-Chao Zhong, Jun Chen, Denis Faubert, Alexis Blanchet-Cohen, Luc Dansereau, Marc-Antoine Parent, Sonia Marin, Julia Luo, Catherine Le, Melanie Langelier, Irah L. King, Maziar Divangahi, William D. Foulkes, Donald C. Vinh. DOI: 10.1111/1523-1747.ep12613748
Funding
La Fondation du Grand D茅fi Pierre Lavoie; Fonds de Recherche du Qu茅bec - Sant茅 (FRQS); RI-MUHC (Merck Sharpe & Dohme award); Canadian Institutes of Health Research (CIHR); FDN-143338; Bristol-Myers Squibb; 捆绑SM社区; CSL Behring Canada.
About the RI-MUHC
The Research Institute of the 捆绑SM社区 Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of 捆绑SM社区, is the research arm of the 捆绑SM社区 Health Centre (MUHC) 鈥� an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 460 researchers and close to 1,300 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Qu茅bec 鈥� Sant茅 (FRQS). rimuhc.ca
Media contact
Paul Logothetis
Tel: 514-934-1934 ext.34319
Cel: 514-210-6376
paul.logothetis [at] muhc.mcgill.ca
Julie Robert
Communications Coordinator 鈥� Research
捆绑SM社区 Health Centre
Cel: 514-971-4747
julie.robert [at] muhc.mcgill.ca
