Address correspondence and reprint requests to Dr. F. Zara at Laboratory of Human Genetics, E.O. Ospedale Galliera, Via Volta 10r–16128–Genova, Italy. E-mail: [email protected]

Read the full text

About

PDF

Tools

Share a link

Email
Wechat
Bluesky

Abstract

Summary: Purpose: Mutations in the voltage-gated sodium channel subunit gene SCN1A have been associated with febrile seizures (FSs) in autosomal dominant generalized epilepsy with febrile seizures plus (GEFS⁺) families and severe myoclonic epilepsy of infancy. The present study assessed the role of SCN1A in familial typical FSs.

Methods: FS families were selected throughout a collaborative study of the Italian League Against Epilepsy. For each index case, the entire coding region of SCN1A was screened by denaturant high-performance liquid chromatography. DNA fragments showing variant chromatograms were subsequently sequenced.

Results: Thirty-two FS families accounting for 91 affected individuals were ascertained. Mutational analysis detected a single coding variant (A3169G) on exon 16. The extended analysis of all family members and 78 normal controls demonstrated that A3169G did not contribute to the FS phenotype.

Conclusions: Our study demonstrated that SCN1A is not frequently involved in common FSs and suggested the involvement of specific FS genes.

REFERENCES

1 Escayg A, MacDonald BT, Baulac S, et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS. Nat Genet 2000; 24: 343–5.
10.1038/74159
CAS PubMed Web of Science® Google Scholar
2 Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na⁺-channel α1 subunit gene SCN1B. Nat Genet 1998; 19: 366–70.
Google Scholar
3 Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68: 1327–32.
10.1086/320609
CAS PubMed Web of Science® Google Scholar
4 Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus: a genetic disorder with heterogeneous clinical phenotypes. Brain 1997; 120: 479–90.
10.1093/brain/120.3.479
PubMed Web of Science® Google Scholar
5 Singh R, Scheffer IE, Crossland K, et al. Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol 1999; 45: 75–81.
10.1002/1531-8249(199901)45:1<75::AID-ART13>3.0.CO;2-W
CAS PubMed Web of Science® Google Scholar
6 Wallace RH, Scheffer IE, Barnet S, et al. Neuronal sodium-channel α1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet 2000; 68: 859–65.
Web of Science® Google Scholar
7 Escayg A, Heils A, MacDonald BT, et al. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus and prevalence of variants in patients with epilepsy. Am J Hum Genet 2000; 68: 866–73.
Web of Science® Google Scholar
8 Wallace RH, Marini C, Petrou S, et al. Mutant GABA_A receptor γ₂-subunit in childhood absence epilepsy and febrile seizures. Nat Genet 2001; 28: 49–52.
10.1038/ng0501-49
CAS PubMed Web of Science® Google Scholar
9 Sugawara T, Tsurubuchi Y, Agarwala KL, et al. A missense mutation of the Na⁺ channel α_II subunit gene Na_v1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci U S A 2001; 98: 6384–9.
Web of Science® Google Scholar
10 Baulac S, Huberfeld G, Gourfinkel-An I, et al. First genetic evidence of GABA_A receptor dysfunction in epilepsy: a mutation in the α2-subunit gene. Nat Genet 2001; 28: 46–8.
CAS PubMed Web of Science® Google Scholar
11 Nakayama J, Hamano K, Iwasaki N, et al. Significant evidence for linkage of febrile seizures to chromosome 5q14-q15. Hum Mol Genet 2000; 9: 87–91.
10.1093/hmg/9.1.87
CAS PubMed Web of Science® Google Scholar
12 Wallace RH, Berkovic SF, Howell RA, et al. Suggestion of a major gene for familial febrile convulsions to 8q13-21. J Med Genet 1996; 33: 308–12.
10.1136/jmg.33.4.308
CAS PubMed Web of Science® Google Scholar
13 Johnson EW, Dubovsky, Rich SS, et al. Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest. Hum Mol Genet 1998;7:63–7.
Google Scholar
14 Baulac S, Picard F, Herman A, et al. Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31. Ann Neurol 2001; 49: 786–92.
10.1002/ana.1014
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume43, Issue5

May 2002

Pages 559-562

Lack of SCN1A Mutations in Familial Febrile Seizures

Abstract

REFERENCES

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Lack of SCN1A Mutations in Familial Febrile Seizures

Abstract

REFERENCES

Citing Literature

References

Related

Information