Clinical exome sequencing identifies a novel variant in SCN1A gene in a Moroccan patient with Dravet syndrome

Abstract

Dravet syndrome (DS) is a rare genetic epilepsy syndrome inherited by an autosomal dominant manner. It’s characterized by occurrence of protracted febrile seizures (FS) followed by development of multiple seizure types and psychomotor retardation. Early DS diagnosis in a child with FS facilitate institution of appropriate treatment. In clinical practice, Exome-Sequencing (ES) become a powerful approach for molecular diagnosis in genetic epilepsies.
 A 3-year-old Moroccan girl, born to non-consanguineous parents, was diagnosed with DS. The FS (10-15min) began in the first year of life (10months) followed by fever (40°C) and sleep problems. MRI, EEG and psychomotor development were normal. Positive family history of FS was reported in the father. The focal myoclonic seizures developed during the second-year were prolonged, repeated and resistant to treatments. ES has shown a novel heterozygous missense variant [c.4265A>T (p. Tyr1422Phe)] in exon 21 of SCN1A gene that encodes the type-1-subunit of neuronal voltage-gated sodium channel which regulate neuronal excitability. This variant has been predicted to be probably damaging by in-silico analysis. Genetic counselling is recommended for all families with SCN1A mutation. More analyses are needed to identify the phenotypic features of this novel variant in order to establish an effective care management.
 Keywords: Dravet syndrome, Exome sequencing, SCN1A, Moroccan patient.