Phenotypic Heterogeneity and Genotypic Spectrum of Primary
Immunodeficiencies with Whole Exome Sequencing in a Thai Patient Cohort
Abstract
Background: Primary immunodeficiency diseases (PIDs) comprise more than
400 rare diseases with potential life-threatening conditions. Clinical
manifestations and genetic defects are heterogeneous and diverse among
populations. Here, we aimed to characterize the clinical, immunological
and genetic features of Thai pediatric patients with PIDs. The use of
whole exome sequencing (WES) in diagnosis and clinical decision making
was also assessed. Methods: 36 unrelated patients with clinical and
laboratory findings consistent with PIDs were recruited from January
2010 to December 2020. WES was performed to identify the underlying
genetic defects. Results: The median age of disease onset was 4 months
(range; 1 month to 13 years) and 24 were male (66.7%). Recurrent
sinopulmonary tract infection was the most common clinical presentation
followed by septicemia, and severe pneumonia. Using WES, we successfully
identified the underlying genetic defects in 18 patients (50%). Of the
20 variants identified, six have not been previously described (30%).
According to the International Union of Immunological Societies (IUIS),
38.9% of these detected cases (7/18) were found to harbor variants
associated with genes in combined immunodeficiencies with associated or
syndromic features (Class II). Conclusion: The diagnostic yield of WES
in this patient cohort was 50%. Six novel genetic variants in PID genes
were identified. The clinical usefulness of WES in PIDs was
demonstrated, emphasizing it as an effective diagnostic strategy in
these genetically heterogeneous disorders.