జర్నల్ ఆఫ్ జెనెటిక్ సిండ్రోమ్స్ & జీన్ థెరపీ
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నైరూప్య

Can the p.Thr1174Ser Mutation in SCN1A Gene Shape Genetic Background in Epileptic Encephalopathies?

Dorota Hoffman Zacharskaa, Iwona Terczynska, Paulina Górka-Skoczylasa, Anna Winczewska Wiktor, Tomasz Mazurczak, Jolanta Góral, Agnieszka Charzewska, Kinga Duszyc and Elzbieta Szczepanik

Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures plus (GEFS+) are very often caused by mutations in the SCNA1A gene. These mutations also have been identified in families with migraine phenotypes, supporting the link between migraine and epilepsy. The SCN1A substitution p.Trp1174Ser has been reported as a cause of familial migraine and familial mixed phenotypes with seizures / hemiplegic migraine. We present this mutation as a causative factor of familial GEFS+ syndrome, but also as a factor potentially changing the phenotypes of the epileptic encephalopathies caused by mutations in the SCN1A, ARX or PCDH19 genes. Substitution p.Trp1174Ser was identified in five probands clinically diagnosed as spectrum of GEFS+ or DS. As it has not been regarded as significant for the epileptic encephalopathy, they underwent additional testing according to the revised phenotypes. Probands were finally diagnosed with GEFS+ (p.Trp1174Ser SCN1A mutation only) and epileptic encephalopathies: DS (p.Arg712* and p.Arg1245* in SCN1A), Epilepsy and Mental Retardation Limited to Females (p.Asp155Tyr in PCDH19) and atypical West Syndrome (del79nt IVS4/Ex5 in ARX). This study indicates a complex involvement of some SCN1A mutations in epilepsies / epileptic encephalopathies also as a modifying factor with the SCN1A, PCDH19, ARX and possibly mutations in other genes. In cases with atypical or "plus" course or more severe course the possible involvement of other genetic factors should always be considered. Additional modifiers identification may influence on clinical prognosis, patient management and genetic counselling.