ライフサイエンスコーパス: GEFS

1 Here we report that knock-in of a GEFS+ SCN1A mutation (K1270T) into the Drosophila sodium

2 ABAergic interneurons in the brains of adult GEFS+ flies reveal a novel cellular mechanism underlying

3 he clinical variability observed in SMEI and GEFS+.

4 Borderline GEFS+ families shared many characteristics of classical

5 th classical GEFS+; families with borderline GEFS+; families with unclassified epilepsy; and families

6 familial epilepsy and demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1

7 orylation and its association with the cdc42 GEFS, DOCK180 and alpha/betaPIX.

8 ies shared many characteristics of classical GEFS+ families-such as prominent febrile seizures plus a

9 pes were identified: families with classical GEFS+; families with borderline GEFS+; families with unc

10 (K289M)) in an inheritable form of epilepsy (GEFS+, generalized epilepsy with febrile seizures plus)

11 distinct from those previously observed for GEFS+ and SMEI, suggesting possible, but complex, genoty

12 e examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch

13 fers a deleterious gain-of-function in human GEFS+ patients.

14 uronal excitability, we introduced the human GEFS+ mutation SCN1A-R1648H into the orthologous mouse g

15 thic generalised epilepsies predominating in GEFS+) and double the prevalence of migraine.

16 This work has confirmed the role of SCN1A in GEFS+, by identification of a novel mutation in a previo

17 ation) may contribute to febrile seizures in GEFS+ and perhaps normal individuals.

18 Inheritance of GEFS+ is dominant, but the underlying cellular mechanism

19 Unlike three other GEFS+ alleles that we recently characterized, neither R1

20 In contrast, two other GEFS+ mutations (A1685V and V1353L) and L986F, an SMEI-a

21 ralized epilepsy with febrile seizures plus (GEFS+ type 2), severe myoclonic epilepsy of infancy (SME

22 ralized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI).

23 ralized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI).

24 ralized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy.

25 ralized epilepsy with febrile seizures plus (GEFS+) associated with C-terminal mutations in other NaV

26 ralized epilepsy with febrile seizures plus (GEFS+) have been identified previously in the SCN1A gene

27 ralized epilepsy with febrile seizures plus (GEFS+) is caused by missense mutations in NaV1.1 channel

28 ralised epilepsy with febrile seizures plus (GEFS+) is the most studied familial epilepsy syndrome.

29 genetic epilepsy with febrile seizures plus (GEFS+) spectrum disorders in humans, and Scn1b-null mice

30 ralized epilepsy with febrile seizures plus (GEFS+) type 2.

31 ralized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilep

32 ralized epilepsy with febrile seizures plus (GEFS+), created a loss of function with homozygous expre

33 ralized epilepsy with febrile seizures plus (GEFS+),(7) severe myoclonic epilepsy of infancy, and fam

34 genetic epilepsy with febrile seizures plus (GEFS+).

35 ralized epilepsy with febrile seizures plus (GEFS+).

36 ralized epilepsy with febrile seizures plus (GEFS+).

37 genetic epilepsy with febrile seizures plus (GEFS+).

38 Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)).

39 l excitability, in contrast to most previous GEFS+ sodium channel mutations, which have changes predi

40 One previously reported GEFS+ mutation (I1656M) and an additional novel allele (

41 channel genes can produce the same syndrome, GEFS+, while individuals with the same allele can experi

42 d persistent sodium current exhibited by the GEFS+ mutant R1648H.

43 ent current similar to that observed for the GEFS+ mutant R1648H.

44 ypothesize that a likely explanation for the GEFS+ phenotype is a dominant-negative suppression of wi

45 e seizures, intermediate impairment leads to GEFS+ epilepsy, and severe or complete loss of function

46 a2gamma2L(K289M)) GABA(A) receptor linked to GEFS+.

47 with a clinical presentation consistent with GEFS+.

48 Most families with GEFS+ have no identified causal mutation, and so predict

49 ation W1204R was identified in a family with GEFS+.