AB026. SCN1A mutational analysis in 20 Vietnamese children with Dravet syndrome

Background: Dravet syndrome is one of the most catastrophic types of epilepsy in infants. It is found that 70-80% of cases of Dravet syndrome are caused by mutations in SCN1A, the gene encoding alpha-1 subunit of the sodium channel. Mutations of the SCN1A gene have an autosomal dominant inheritance pattern. To date, over 1,000 SCN1A mutations have been reported all over the world, however, no SCN1A mutation studies have been performed in the Vietnamese population, and genetic characteristics of Vietnamese Dravet patients are not yet clear. In this study, we analyzed SCN1A gene in 20 Vietnamese patients with clinical features of Dravet syndrome at Children’s Hospital 2, Ho Chi Minh City, Vietnam.

Methods: Direct sequencing and multiple ligation-dependent probe amplification (MLPA) were performed to screen the entire coding regions as well as exon-intron boundaries of the gene.

Results: Fourteen mutations (14/20; 70%) were identified including 13 point mutations detected by PCR-Sequencing and 1 large deletion mutation spanning nearly whole exon 7 detected by MLPA. Five mutations were classified as truncations (2 frameshift and 3 nonsense mutations) and 9 were classified as missense mutations. There were 7 mutations were localized at pore-forming loop (connecting S5-S6); 5 mutations were localized at cytoplasmic loops (connecting 2 nearby homologous domains), 1 mutations were localized at transmembrane segments, and 1 mutation in a intronic region. Nine of these 14 SCN1A mutations were novel and parental DNA analysis for the identified mutations in 11 available cases show that all of the mutations were de nono. Besides well-known genotype–phenotype correlations, our study results strongly suggests the existence of modifying factors.

Conclusions: The proportion of SCN1A mutations among Vietnamese Dravet patients in this study appeared to be consistent with other populations (70%). Our study also expands the spectrum of SCN1A mutations and confirms the current understanding of genotype–phenotype correlations.

Keywords: Dravet syndrome; SCN1A; Vietnamese