Sodium channel α1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms
Abstract
Background: Mutations in SCN1A, the gene encoding the α1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS+ in a significant proportion of patients with SMEI. Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy.
Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS.
Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI.
Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS+ could interact with other loci to cause SMEI in cases with a family history of GEFS+. This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.
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References
1.
Ptacek LJ, George AL Jr, Griggs RC, et al. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell . 1991; 67: 1021–1027.
2.
Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell . 1995; 80: 805–811.
3.
Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel β1 subunit gene SCN1B. Nat Genet . 1998; 19: 366–370.
4.
Wallace RH, Scheffer IE, Parasivam G, et al. Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. Neurology . 2002; 58: 1426–1429.
5.
Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain . 1997; 120: 479–490.
6.
Singh R, Scheffer IE, Crossland K, Berkovic SF. Generalized epilepsy with febrile seizures plus: a common, childhood onset, genetic epilepsy syndrome. Ann Neurol . 1999; 45: 75–81.
7.
Escayg A, MacDonald BT, Meisler MH, et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+. Nat Genet . 2000; 24: 343–345.
8.
Escayg A, Heils A, MacDonald BT, Haug K, Sander T, Meisler MH. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus—and prevalence of variants in patients with epilepsy. Am J Hum Genet . 2001; 68: 866–873.
9.
Wallace RH, Scheffer IE, Barnett S, et al. Neuronal sodium-channel α1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet . 2001; 68: 859–865.
10.
Abou–Khalil B, Ge Q, Desai R, et al. Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation. Neurology . 2001; 57: 2265–2272.
11.
Sugawara T, Mazaki–Miyazaki E, Ito M, et al. Na(v)1.1 mutations cause febrile seizures associated with afebrile partial seizures. Neurology . 2001; 57: 703–705.
12.
Sugawara T, Tsurubuchi Y, Agarwala KL, et al. A missense mutation of the Na+ channel αII subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci USA . 2001; 98: 6384–6389.
13.
Heron S, Crossland K, Andermann E, et al. Sodium-channel defects in benign familial neonatal–infantile seizures. Lancet . 2002; 360: 851.
14.
Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet . 2001; 68: 1327–1332.
15.
Dravet C. Les epilepsies graves de l’enfant. Vie Med . 1978; 8: 543–548.
16.
Dravet C, Roger J, Bureau M, Dalla Bernardina M. Myoclonic epilepsies in childhood. In: Akimoto H, Kazamatsuri H, Seino M, Ward A, eds. Advances in epileptology. XIIIth Epilepsy International Symposium. New York: Raven Press, 1982: 135–141.
17.
Dravet C, Bureau M, Roger J. Severe myoclonic epilepsy in infants. In: Roger J, Dravet C, Bureau M, Dreifuss FE, Wolf P, eds. Epileptic syndromes in infancy, childhood and adolescence. London: Libbey, 1985: 58–104.
18.
Singh R, Andermann E, Whitehouse WPA, et al. Severe myoclonic epilepsy of infancy: extended spectrum of GEFS+? Epilepsia . 2001; 42: 837–844.
19.
Veggiotti P, Cardinali S, Montalenti E, Gatti A, Lanzi G. Generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy: a case report of two Italian families. Epileptic Disord . 2001; 3: 29–32.
20.
Sugawara T, Mazaki–Miyazaki E, Fukushima K, et al. Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Neurology . 2002; 58: 1122–1124.
21.
Ohmori I, Ouchida M, Ohtsuka Y, Oka E, Shimizu K. Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun . 2002; 295: 17–23.
22.
Fujiwara T, Sugawara T, Mazaki–Miyazaki E, et al. Mutations of sodium channel α subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic–clonic seizures. Brain . 2003; 126: 531–546.
23.
Harkin LA, Bowser DN, Dibbens L, et al. Truncation of the GABAA receptor γ2 subunit in a family with generalized epilepsy with febrile seizures plus. Am J Hum Genet . 2002; 70: 530–536.
24.
Vigevano F, Fusco L, Cusmai R, Claps D, Ricci S, Milani L. The idiopathic form of West syndrome. Epilepsia . 1993; 34: 743–746.
25.
Stromme P, Mangelsdorf ME, Shaw MA, et al. Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet . 2002; 30: 441–445.
26.
Stromme P, Mangelsdorf ME, Scheffer IE, Gecz J. Infantile spasms, dystonia, and other X-linked phenotypes caused by mutations in Aristaless related homeobox gene, ARX. Brain Dev . 2002; 24: 266–268.
27.
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia . 1989; 30: 389–399.
28.
Engel J Jr . A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia . 2001; 42: 796–803.
29.
Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron . 2000; 26: 13–25.
30.
Garrido JJ, Fernandes F, Giraud P, et al. Identification of an axonal determinant in the C-terminus of the sodium channel Na(v)1.2. EMBO J . 2001; 20: 5950–5961.
31.
Mantegazza M, Yu FH, Catterall WA, Scheuer T. Role of the C-terminal domain in inactivation of brain and cardiac sodium channels. Proc Natl Acad Sci USA . 2001; 98: 15348–15353.
32.
Rivolta I, Abriel H, Tateyama M, et al. Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem . 2001; 276: 30623–30630.
33.
Sugama M, Oguni H, Fukuyama Y. Clinical and electroencephalographic study of severe myoclonic epilepsy in infancy (Dravet). Jpn J Psychiatry Neurol . 1987; 41: 463–465.
34.
Hurst DL. Severe myoclonic epilepsy of infancy. Pediatr Neurol . 1987; 3: 269–272.
35.
Benlounis A, Nabbout R, Feingold J, et al. Genetic predisposition to severe myoclonic epilepsy in infancy. Epilepsia . 2001; 42: 204–209.
36.
Baulac S, Huberfeld G, Gourfinkel–An I, et al. First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene. Nat Genet . 2001; 28: 46–48.
37.
Wallace RH, Marini C, Petrou S, et al. Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet . 2001; 28: 49–52.
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Publication History
Received: January 13, 2003
Accepted: May 29, 2003
Published online: September 22, 2003
Published in print: September 23, 2003
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