Monogenic basis of young-onset cryptogenic stroke: a multicenter study.

Area of Science:

• Genetics
• Neurology
• Cardiology

Background:

• Stroke incidence is rising among young adults.
• The monogenic basis of cryptogenic stroke in this demographic remains under investigation.

Purpose of the Study:

• To investigate the monogenic causes of cryptogenic stroke in young adults.
• To identify specific genes and associated disease categories linked to young-onset stroke.

Main Methods:

• A multicenter study enrolled cryptogenic stroke patients under 55 years old and controls.
• Targeted next-generation sequencing (NGS) was performed using a 551-gene panel.
• Rare variants were classified as pathogenic or of unknown significance.

Main Results:

• Pathogenic variants were detected in 53.3% (16/30) of young cryptogenic stroke patients.
• The most prevalent mutated genes included NOTCH3, PRKAG2, and RYR2.
• Mutations in cardiogenic disease genes were most frequent (55.6%), followed by small-vessel disease and coagulation disorder genes.

Conclusions:

• Nearly half of young-onset cryptogenic stroke patients harbor pathogenic variants.
• Genes associated with cardiogenic diseases are frequently implicated.
• Findings suggest potential for refined diagnostic approaches and clinical decision-making.