Objective To study SCN1A gene mutations and their inheritance in patients with Dravet syndrome (DS), and to analyze the phenotypes of their family members.
Methods Genomic DNA was extracted from peripheral blood samples from DS patients and their parents. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).
Results 547 DS patients were collected, SCN1A gene mutations were identified in 379 patients (69.3%), which included 179 missense mutations (47.2%), 78 nonsense mutations (20.6%), 77 frameshift mutations (20.3%), 37 splice site mutations (9.8%), and 8 cases with SCN1A gene fragment deletions or duplications (2.1%). Of 379 DS patients, the parents of 354 DS patients were further analyzed, the de novo mutations accounted for 92.9%, inherited mutations accounted for 7.1%, and in 5 of the latter families, the SCN1A-positive parent carried a somatic mutations mosaicism. For the 25 parents carrying SCN1A mutations, 1 had DS, 11 had febrile seizures plus, 9 had febrile seizures, whilst 4 were normal.
Conclusions The mutation rate of SCN1A in DS patients is high. Most mutations are of missense and truncation mutations (including nonsense mutation and frameshift mutation). Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few are inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations can be severe, mild or normal, and a mosaic transmitting parent always shows mild or normal.
TIANXiaojuan, ZHANGYuehua, YANGXiaoling, XUXiaojing, LIUAijie, LIUXiaoyan, YANGZhixian, WUYe, JIANGYuwu, WUXiru. Genetic characteristics of SCN1A mutations in 547 Dravet syndrome. Journal of Epilepsy, 2016, 2(1): 3-8. doi: 10.7507/2096-0247.20160001