GNAO1 encephalopathies: a step towards finer diagnosis
GNAO1 encephalopathies are rare but serious genetic diseases due to mutations in the gene that encodes for the brain protein Gαo. Symptoms vary widely from one patient to another - from developmental delays to severe epilepsy and movement disorders. This highly variability makes it hard to predict its gravity and progression.
A promising biomarker for disease severity
Last year, researchers from the laboratory of Prof. Vladimir Katanaev were able for the first time to predict the severity of GNAO1 encephalopathies. They showed that the more strongly the mutated Gαo binds to Ric8 proteins, the more severe are the symptoms. To move further, the team expanded their investigation to new patient cases spanning the full range of clinical symptoms.
New patient cases strength the link
, they investigated two children, one from France, another from China, showing severe early-onset symptoms. As predicted, their mutated Gαo protein exhibited a strong, abnormal interaction with Ric8 proteins. Then, , the team turned to the milder side of the spectrum and analyzed two Italian patients with less severe symptoms. In these cases, the Gαo–Ric8 interaction was much weaker, again consistent with the proposed biomarker.
Toward finer diagnosis
By investigating new genetic mutations and confirming a biomarker linked to disease severity, these findings offer a clearer view of how GNAO1 encephalopathies work. It offers a valuable step towards better clinical predictions and more personalized treatment options for patients.