A Comprehensive Analysis of FLG Mutations in Children with Atopic Dermatitis: Clinical Patterns and Genetic Diversity

Objective: Atopic dermatitis (AD) is a prevalent chronic skin disorder that manifests in early childhood. It is characterised by a heterogeneous clinical presentation and a multifactorial etiology. Early-onset and severe AD have been closely linked to loss-of-function mutations in the FLG gene, which codes for the epidermal barrier protein filaggrin. The therapeutic ramifications of these results are not yet fully understood, yet a significant proportion of individuals continue to be wild-type or to carry rare variations of undetermined significance (VUS). In addition to examining the distribution and phenotypic impact of FLG mutations, including both likely pathogenic and unclear alterations, the present study sought to assess the clinical characteristics of paediatric AD.Methods: The evaluation of 67 children (aged 0–5) with clinically confirmed AD was conducted using laboratory data, environmental history, and SCORAD severity levels. Utilising a targeted next-generation sequencing (NGS) technique, the FLG gene was comprehensively sequenced.Results: Amongst the sample of 28 patients (41.8%) who exhibited FLG variations, 10 cases were found to contain mutations with the potential to be deleterious, while 18 cases revealed Variants of Uncertain Significance (VUS). Elevated levels of immunoglobulin E (IgE) and moderate-to-severe atopic dermatitis (AD) were more frequently associated with likely pathogenic allergen carriers. While wild-type patients also exhibited severe cases, individuals with VUS carriers demonstrated a range of phenotypes, thereby emphasising the significance of non-genetic variables.Conclusion: This study suggests that certain VUS may possess developing clinical significance and reinforces the role of FLG mutations in paediatric AD. A combined clinical and molecular evaluation may enhance illness stratification and facilitate the development of individualised treatment plans.