Phenotype and gene mutation screening in familial Dravet syndrome

Abstract

Objective To summarize the phenotype and gene mutation in familial Dravet syndrome (DS) and provide guidance for genetic counseling. Methods The clinical data and peripheral blood DNA samples of familial DS patients and their parents were collected from February 2005 to March 2016 in Department of Pediatrics, Peking University First Hospital.SCN1A mutations were screened by adopting Sanger sequencing and multiple ligation-dependent probe amplification (MLPA). Next generation sequencing(NGS) for epilepsy-related gene-panel was applied to SCN1A mutation-negative patients and their parents. Results In 6 DS families, each consisted of 2 DS patients.Two families had siblings affected, one family involved mother and son, one family involved mother and daughter, one had monozygotic twins affected and one had dizygotic twins involved.SCN1A mutations were identified in 5 DS families(R101Q, R377X, L390P, F1486L, R1245X). Among the 5 DS families with SCN1A mutations, 3 families were identified as inherited heterozygous mutations, and phenotypes of the transmitting parents were DS or febrile seizure plus(FS+ ). While 2 families were highly suspected of parental mosaicism from the results of Sanger sequencing, and the transmitting parents had no history of febrile and epileptic seizures.No SCN1A and other DS-related gene mutation that had been reported was found in the remaining family and the phenotype of parents were normal. Conclusions The affected members of familial DS could be exhibited as one parent and child affected, or sibling pairs, monozygotic or dizygotic twins involved.The majority of familial DS carried SCN1A mutations, while others might carry other DS-causing gene mutation.The mutations of familial DS patients were inherited from one parent, including a mosaic transmitting parent.The phenotypes of the parent carrying SCN1A mutation could be DS, FS+ or normal. Key words: Dravet syndrome, familial; SCN1A gene; Mosaicism