[P1-1~141] Poster Presentation 1

[P1-96] Somatic Mosaic Deletions Involving SCN1A Cause Dravet Syndrome

^○Tojo NAKAYAMA^{1, 2} (1.Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan, 2.Division of Genetics and Genomics, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA)

Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a subset of parents of children with Dravet syndrome. However, because mosaic deletions are inherently challenging to detect using standard screening methods, no previous studies have investigated mosaic microdeletions involving SCN1A in a Dravet syndrome cohort. Here, we report recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed with mild Dravet syndrome. Through the evaluation of 237 affected individuals with Dravet syndrome who did not show SCN1A or PCHD19 mutations in prior sequencing analyses, we identified two children with mosaic microdeletions covering the entire SCN1A region. The allele frequency of the mosaic deletions estimated by multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) was 25%–40%, which was comparable to the mosaic ratio in lymphocytes and buccal mucosa cells observed by fluorescence in situ hybridization (FISH) analysis. Prevalence of SCN1A mosaic deletion is estimated 0.8% (2/237) of Dravet syndrome with negative for SCN1A and PCDH19 mutations. This study reinforces the importance of somatic mosaicism caused by copy number variations in disease-causing genes. Somatic deletions in SCN1A should be considered in cases with Dravet syndrome when standard screenings for SCN1A mutations are apparently negative for mutations.