RESUMEN
While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8â¯%. Through systematic reanalysis, we identified variants of interest in 5.2â¯% of undiagnosed patients, with 76.7â¯% being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2â¯% of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4â¯%). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated.
RESUMEN
BACKGROUND: To our knowledge, in Asia, data on utility of allergy tests in management of eosinophilic esophagitis are lacking. The objective of our study was to determine the role of allergy evaluation in management of Saudi children with eosinophilic esophagitis. METHODS: Children diagnosed as having eosinophilic esophagitis during the period from 2009 to 2012 were referred to an allergist for allergy evaluation. The allergy evaluation consisted of total IgE level, radio-allergosorbent assay, and skin prick test. Depending on the results of the allergy tests, a restricted or elemental diet was established. Swallowed fluticasone inhaler was prescribed to patients who rejected or failed to respond to the diet. Clinical, endoscopic, and histological evaluation was performed in 8 weeks to assess response. RESULTS: Eighteen children with eosinophilic esophagitis were included (13 males; mean age 5 years, range 1-11). Sensitization to foods was demonstrated in 14 patients: 4 with a positive test for a single food (28.5%), 1 for 2 food allergens (7%), and 9 for ≥3 food allergens (64.5%). The most common food allergens were milk, soybean, wheat, egg, and nuts. Three young children out of the total 14 patients responded to elemental formula. Four of the 10 older children on the allergy testing guided-dietary restriction achieved partial remission and the remaining 6 did not respond. All 10 patients responded to a swallowed fluticasone inhaler. CONCLUSION: Although food sensitizations in Saudi children with eosinophilic esophagitis are common, the allergy tests had limited predictive value for the response to dietary elimination.