Targeted Filaggrin Gene (FLG) Sequencing: A Pilot Study among Indian Children with Atopic Dermatitis.

Background: Filaggrin deficiency causes early-onset atopic dermatitis (AD), extrinsic AD, persistent and severe disease, palmoplantar hyper linearity, keratosis pilaris, and increased risk of hand eczema. There is a paucity of data on the prevalence and types of variation in the filaggrin gene (FLG) in the Indian population.

Aim and objectives: To study the prevalence and characteristics of filaggrin mutations in Indian children affected with AD and to attempt a genotype-phenotype correlation.

Materials and methods: A pilot study was done among Indian children with AD aged 4-16 years, attending the Pediatric Dermatology outpatient department between February and September 2022 (7 months). Long-range polymerase chain reaction target enrichment and next-generation sequencing were used to sequence the complete FLG gene from peripheral blood samples. The identified variants were analyzed and categorized.

Results: Among the 30 recruited children with AD, 28 genetic variants in exon 3 of FLG were found in 19 (63%) patients. These variants were classified as pathogenic (6, 21.4%), likely pathogenic (3, 10.7%), benign (16, 57.1%), and variant of uncertain significance (3, 10.7%). Among the 9 significant variants, 4 (45%) were novel. Although the patients with filaggrin variants had a higher prevalence of positive family history of atopy, other allergic diseases in the child, higher IgE levels, and a higher percentage of severe AD, the difference was not statistically significant.

Limitation: Small sample size.

Conclusion: Significant FLG null variants were identified in 23% (among which 45% were novel) of Indian children with AD. The spectrum of identified variants did not reflect the known FLG hotspots from other ethnicities, indicating the need for larger studies to determine the relevant hotspots in the Indian population.