Enhancing Primary Immunodeficiency Diagnosis: Findings From Targeted Genetic Testing in a Turkish Cohort

Area of Science:

• Immunology
• Genetics
• Paediatrics

Background:

• Primary immunodeficiency disorders (PIDDs) are genetic conditions causing recurrent infections and immune dysregulation.
• Clinical evaluation is crucial, but genetic testing is key for diagnosis and management.
• The Jeffrey Modell Foundation's 'Jeffrey's Insights' programme facilitates genetic evaluation.

Purpose of the Study:

• To evaluate the diagnostic yield and clinical utility of targeted gene panel testing in patients with suspected PIDDs.
• To assess the impact of genetic findings on PIDD classification and patient care.

Main Methods:

• A cross-sectional study of 104 patients with suspected PIDDs evaluated between 2022-2024.
• Targeted gene panel testing was performed on patients without prior genetic diagnosis.
• Clinical phenotypes were correlated with identified genetic variants.

Main Results:

• Genetic variants consistent with clinical phenotypes were found in 72 of 104 patients.
• Pathogenic/likely pathogenic variants identified in 41.3% (57.7% including VUS with high CADD scores).
• Genetic findings led to reclassification of IUIS categories in 25% of cases; failure to thrive and low B cells associated with diagnosis.

Conclusions:

• Targeted gene panels are valuable tools for diagnosing and classifying PIDDs.
• Genetic testing enhances precision in patient care and enables tailored therapeutic strategies.
• Findings highlight the importance of genetic analysis in managing complex immune deficiencies.