Unveiling the Secrets: A Breakthrough in Understanding a Rare Bone Disease.

 

A team of researchers, led by McGill, has uncovered a significant breakthrough shedding light on the genetic origins of a rare skeletal disorder. Their study, featured in Nature Communications, discloses that a flaw in a specific gene, Matrix Gla protein (MGP), may lead to a disorder impacting the connective tissues supporting the body's structure.

MGP, a unique protein present in blood vessels and cartilage, plays a role in preventing the hardening of these tissues. Complete absence of MGP can result in Keutel syndrome, where tissues calcify, causing skeletal and blood vessel issues. Yet, in this instance, the observed variance in the MGP gene differs from Keutel syndrome, both in its manifestation in individuals and at the cellular and molecular levels.

The study highlights four individuals from different families with a slight alteration in their MGP gene, resulting in a modified protein and a specific bone disorder. Testing these genetic changes on mice revealed similar bone issues in both species. The altered protein, unlike the normal one, fails to exit cells, inducing stress in the endoplasmic reticulum. Cartilage cells producing the altered protein succumb to stress, leading to bone abnormalities.

This research not only enhances comprehension of the genetic factors contributing to skeletal dysplasia but also opens avenues for potential therapeutic interventions. Understanding the crucial role of the MGP gene in skeletal development provides optimism for improved diagnosis and treatment of those affected by this rare condition.

Professor Monzur Murshed, the senior author, emphasizes the broader impact, stating that increased awareness of their work may encourage affected individuals to consult clinicians and researchers. Post-publication, they have already received inquiries from a clinician examining another person with skeletal dysplasia and the same MGP gene mutation, promising further research and advancements in disease treatment.