Evaluation of burden of SCN1A pathogenicity in North Indian children with Dravet syndrome.

Background: Dravet syndrome is an infantile-onset developmental and epileptic encephalopathy with limited data on the frequency of SCN1A in Indian children. The study aimed to identify and characterize the burden of SCN1A pathogenic variants associated with the Dravet syndrome phenotype through genetic testing in the North Indian population.

Method: In this prospective, cross-sectional study from March 2015 to February 2019, we enrolled 52 children with Dravet syndrome phenotype who underwent genetic testing for SCN1A gene pathogenicity. We assessed variant effect using multiple algorithms, and genetic test results were reported based on recommendations from the American College of Medical Genetics and Genomics guidelines. Additionally, we performed multiplex-ligation dependent probe amplification (MLPA) to detect copy number variations of the SCN1A gene in children without identified genetic pathogenicity (n = 22) and analysed the results using Coffalyser.net.

Results: Of the 52 probands studied, pathogenic variants in the SCN1A gene were identified in 30 children. Among these variants, 11 truncating variants (3 frame-shift variants, 3 intronic variants in splice site regions, and 5 nonsense variants) in 12 unrelated probands, and 17 missense variants in 18 unrelated probands were found. The genetic yield of SCN1A pathogenicity in our cohort (n = 52) was 58 %. Additionally, two of the identified variants were novel. Furthermore, MLPA analysis of the SCN1A gene in 22 children without pathogenic variants yielded no results.

Conclusion: This work represents a genetic analysis of a Dravet syndrome cohort, revealing a 58 % burden of SCN1A variants in children with the Dravet syndrome phenotype from the North Indian population.