MONTREAL, May 29, 2019 – An international research team led by researchers from CHU Sainte-Justine has discovered a rare new genetic disease affecting muscle stem cells. This type of muscle disease, which was unknown until now, specifically affects the survival of this group of cells and leads to progressive muscle weakness that can become severe. The results of the work are being published in the journal Genetics in Medicine.

In this study, the researchers focused on patients with undiagnosed muscle disease that resulted in hypotonia (decreased muscle tone), scoliosis (vertebral deformity) and progressive muscle atrophy (decreased muscle mass). Muscle biopsies on affected individuals showed a decrease in muscle fibre size and the replacement of muscle tissue with fibrous and adipose tissue, but with no cellular necrosis.

In collaboration with international research teams, the researchers identified five individuals with muscle disease of varying severity from four unrelated families, one of which was being treated at Sainte-Justine. The use of new-generation sequencing technologies has made it possible to identify variants likely to cause a loss of function in the PAX7 gene.

The growth and regeneration of skeletal muscles are based on muscle stem cells called satellite cells. "The role of the PAX7 gene has been extensively studied in the laboratory in preclinical models, proving that it is essential for the proper functioning of satellite cells and the development of postnatal muscles, but the consequences for humans have never been established until now," says Professor Nicolas Dumont, a researcher at CHU Sainte-Justine.

"Unlike other muscle diseases, such as muscular dystrophy, which causes muscle fibre fragility and muscle degeneration, our results indicate that a mutation in the PAX7 gene does not affect fibre stability, but rather leads to satellite cells pool exhaustion and consequently to a decrease in muscle growth and regeneration capacity," says Dr. Philippe Campeau, a medical geneticist at CHU Sainte-Justine.

CHU Sainte-Justine: centre of expertise in rare genetic diseases

"This discovery will allow rapid and accurate diagnosis of the disease. Ultimately, it will lead to a better understanding of the underlying mechanisms and will help promote the investigation of pharmacological or gene therapies that can improve the regenerative capacity of satellite cells in affected patients in order to improve their quality of life and better control the disease," adds Dr. Dumont. "CHU Sainte-Justine is a leader in the care of patients suffering with rare diseases and this discovery reinforces its position. It opens a new avenue for the identification of other rare genetic mutations involving muscle stem cells, something that has never been done before," concludes Dr. Jacques L. Michaud, a medical geneticist leading the exome and genome sequencing project at CHU Sainte-Justine and responsible for the patient's genetic investigations at Sainte-Justine from an early age.

About the study

The article "Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy" was published in the journal Genetics in Medicine in May 2019. Nicolas Dumont, Pht, PhD, is a researcher at CHU Sainte-Justine and an assistant professor at the School of Rehabilitation, Université de Montréal. Philippe Campeau, MD, is a medical geneticist, researcher and Deputy Head, Research Axis, of the Musculoskeletal Diseases and Rehabilitation Department, CHU Sainte-Justine, and assistant clinical professor in the Department of Pediatrics, Université de Montréal. The researchers are supported by the Fonds de recherche du Québec – Santé, the Canadian Institutes of Health Research, the Fondation des maladies rares, the CHU Sainte-Justine Foundation, ThéCell Network and Stem Cell Network. This international study involved the collaboration of research teams from Germany, Saudi Arabia, Austria and Canada.