Inborn errors of immunity (IEIs) encompass a heterogeneous group of more than 550 genetic conditions with variable ages of onset. A significant proportion of IEI arises from genetic variants that may not yet be fully elucidated or recorded in existing genomic databases. Molecular diagnoses are achieved in approximately 15–35% of IEI cases, yet in only 9–20% of individuals with predominant antibody deficiencies, particularly in adult cohorts. We aimed to evaluate whole genome sequencing (WGS) diagnostic yield in adults suspected to have IEI. Clinical assessments of the patients were carried out at tertiary medical institutions in Timisoara and Bucharest, Romania. The study cohort included a consecutive series of 21 adult patients (aged 19–60 years) with IEI phenotype, who underwent genetic analysis, using WGS as the first diagnostic approach. A definitive molecular diagnosis was confirmed in only 9.5% (2/21) of the participants, in LRBA and BTK genes. Variants of uncertain significance (VUS) were detected in three patients (13.6%) in TNFRSF13B, COPA, GATA2 genes. For about half of the cohort the onset of the disease was noted in childhood. WGS as a first-line diagnostic strategy in a cohort of adults with IEI yielded a low diagnostic rate. There were significant delays in genetic diagnosis, as half of the cohort experienced childhood-onset symptoms. Results suggest that adult IEI diagnosis remains challenging, necessitating functional studies and longitudinal re-evaluation of genomic data.
Pantea et al. (Fri,) studied this question.