Ceulemans Berten P G M, Claes Lieve R F, Lagae Lieven G
Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium.
Pediatr Neurol. 2004 Apr;30(4):236-43. doi: 10.1016/j.pediatrneurol.2003.10.012.
Mutations in the alpha-subunit of the first neuronal sodium channel gene SCN1A have been described in isolated patients with severe myoclonic epilepsy in infancy or Dravet syndrome and in families with generalized epilepsy with febrile seizures plus. To find phenotype/genotype correlations, we reviewed all published cases of mutations in SCN1A in addition to four new patients reported here. A total of 60 mutations were observed. Approximately 52% (31/60) are truncating mutations correlating with de novo cases of classical Dravet syndrome in 32 of 34 (94%) patients. Missense mutations in the pore-forming part constitute 27% (16/60) and correspond to a classical type in 12 of 16 (75%) patients. Missense mutations in the voltage sensor were present in 12% (7/60) and correlate with a clinical picture ranging from febrile seizures plus to severe myoclonic epilepsy in infancy. Outside these regions missense mutations are rare and account for only 10% (6/60), corresponding mostly with febrile seizures plus. These results illustrate that the clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy, and confirm the clinical experience that severe myoclonic epilepsy in infancy is the most severe form on this spectrum.
首个神经元钠通道基因SCN1A的α亚基突变已在患有婴儿严重肌阵挛性癫痫（Dravet综合征）的散发性患者以及伴有热性惊厥附加症的全身性癫痫家族中有所描述。为了寻找表型/基因型的相关性，我们除了回顾本文报道的4例新患者外，还查阅了所有已发表的SCN1A突变病例。共观察到60种突变。约52%（31/60）为截短突变，与34例患者中32例（94%）的典型Dravet综合征新发病例相关。孔形成部分的错义突变占27%（16/60），在16例患者中的12例（75%）对应于一种典型类型。电压感受器中的错义突变占12%（7/60），与从热性惊厥附加症到婴儿严重肌阵挛性癫痫的临床症状相关。在这些区域之外，错义突变很少见，仅占10%（6/60），大多与热性惊厥附加症相关。这些结果表明，SCN1A突变的临床谱范围从热性惊厥、热性惊厥附加症、较轻类型到婴儿严重肌阵挛性癫痫的典型形式，并证实了临床经验，即婴儿严重肌阵挛性癫痫是该谱中最严重的形式。
