Molecular characteristics of <i>SCN1A</i> mutation causing partial epilepsy with febrile seizures plus_Journal of Epilepsy

Authors：

 MENGHeng ¹ ^* ,  YULu ² ^* , LIBin ³ , KUANGYaoyun ³ , XUAnding ¹ , ZHENGJinou ² ,  LIAOWeiping ³

1. Department of neurology, First Affiliated Hospital of Ji-nan University, Guangzhou 510630, China;
2. Department of neurology, First Affiliated Hospital of Guang-xi Medical University, Nanning 530021, China;
3. Department of neurology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China;

Corresponding author：

LIAOWeiping, Email: wpliao@163.net

Keywords：

Partial epilepsy; Sodium channel; SCN1A gene; Molecular characteristics

DOI：

10.7507/2096-0247.20150014

Video：

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Objective To explore the molecular characteristics of partial epilepsy with febrile seizures plus(PEFS+). Methods We systematically reviewed all SCN1A mutation-related publications that published between Jan.2000 and Dec.2014 on Pubmed and established a database of SCN1A mutations (http://www.gzneurosci.com/SCN1Adatabase/). The characteristics of mutations that cause PEFS+ were analyzed and compared with that of severe myoclonic epilepsy in infancy (SMEI). Results The database included 1, 257 SCN1A mutations, which identified from 1, 727 unrelated cases. In which there were 30 mutations, from 32 unrelated cases, were associated with PEFS+. 76.7% (23/30) mutations were missense, of which 47.8% (11/23) were located on pore region. Significant difference in the percentage of truncation mutation was observed between PEFS+ and SMEI (P < 0.05). There was no significant difference in the percentage of missense mutation that located on the pore region between PEFS+ and SMEI; but the differ significantly in D-value of the missense mutations, which quantified the alteration of amino acid(P=0.042, rank sum test). Conclusions PEFS+, which distinguishes from GEFS+ and SMEI in clinical and molecular characteristics, is a special phenotype of epilepsy that is associated with SCN1A mutations.

Citation： MENGHeng, YULu, LIBin, KUANGYaoyun, XUAnding, ZHENGJinou, LIAOWeiping. Molecular characteristics of SCN1A mutation causing partial epilepsy with febrile seizures plus. Journal of Epilepsy, 2015, 1(2): 101-105. doi: 10.7507/2096-0247.20150014 Copy

1.	廖卫平, 何娜.癫痫基因检测的临床应用及其展望.中华神经科杂志, 2011, 44(17):659-662.
2.	Escayg A, Helse A, Meisler MH, 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, 2001, 68(4):866-873.
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5.	Goldin AL. Evolution of voltage-gated Na+ channels. J Exp Biol, 2002, 205(21):575-584.
6.	Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. J Physiol, 2010, 588(132):1849-1859.
7.	Meng H, Xu HQ, Yu L, et al. The SCN1A mutation database:updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat, 2015, 36(6):573-580.
8.	Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus:a genetic disorder with heterogeneous clinical phenotypes. Brain, 1997, 120 (pt 3):479-490.
9.	Escayg A, MacDonald BT, Meisler MH, et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat Genet, 2000, 24(11):343-345.
10.	Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. J Hum Genet (Am), 2001, 68(7):1327-1332.
11.	Ohmori I, Ouchida M, Ohtsuka Y, et al. Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun, 2002, 295(112):17-23.
12.	Liao WP, Shi YW CL, Deng WY, et al. Partial epilepsy with febrile seizure plus (PEFS+) and novel SCN1A mutations. Epilepsia, 2007, 48(20):130.
13.	Liao WP, Shi YW, Long YS, et al. Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs:associated with loss of function of Na1.1. Epilepsia, 2010, 51(23):1669-1678.
14.	Kumakura A, Ito M, Hata D, et al. Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus. Brain Dev, 2009, 31(10):179-182.
15.	Grantham R. Amino acid difference formula to help explain protein evolution. Science, 1974, 185(12):862-864.
16.	Heng Meng, Bin Tang, Yong-Hong Yi, et al. Splice-site Mutations in SCN1A cause epilepsies with febrile seizures:mechanisms and correlations with clinical severity. Epilepsia, 2013, 54(Suppl 3):192.
17.	Catterall WA. From ionic currents to molecular mechanisms:the structure and function of voltage-gated sodium channels. Neuron, 2000, 26(10):13-25.

1. 廖卫平, 何娜.癫痫基因检测的临床应用及其展望.中华神经科杂志, 2011, 44(17):659-662.
2. Escayg A, Helse A, Meisler MH, 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, 2001, 68(4):866-873.
3. Claes LRF, Deprez L, Suls A, et al. The SCN1A variant database: a novel research and diagnostic tool. Hum Mutat, 2009, 30(2):e904-e920.
4. Goldin AL, Barchi RL, Caldwell JH, et al. Nomenclature of voltage-gated sodium channels. Neuron, 2000, 28(10):365-368.
5. Goldin AL. Evolution of voltage-gated Na+ channels. J Exp Biol, 2002, 205(21):575-584.
6. Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. J Physiol, 2010, 588(132):1849-1859.
7. Meng H, Xu HQ, Yu L, et al. The SCN1A mutation database:updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat, 2015, 36(6):573-580.
8. Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus:a genetic disorder with heterogeneous clinical phenotypes. Brain, 1997, 120 (pt 3):479-490.
9. Escayg A, MacDonald BT, Meisler MH, et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat Genet, 2000, 24(11):343-345.
10. Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. J Hum Genet (Am), 2001, 68(7):1327-1332.
11. Ohmori I, Ouchida M, Ohtsuka Y, et al. Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun, 2002, 295(112):17-23.
12. Liao WP, Shi YW CL, Deng WY, et al. Partial epilepsy with febrile seizure plus (PEFS+) and novel SCN1A mutations. Epilepsia, 2007, 48(20):130.
13. Liao WP, Shi YW, Long YS, et al. Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs:associated with loss of function of Na1.1. Epilepsia, 2010, 51(23):1669-1678.
14. Kumakura A, Ito M, Hata D, et al. Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus. Brain Dev, 2009, 31(10):179-182.
15. Grantham R. Amino acid difference formula to help explain protein evolution. Science, 1974, 185(12):862-864.
16. Heng Meng, Bin Tang, Yong-Hong Yi, et al. Splice-site Mutations in SCN1A cause epilepsies with febrile seizures:mechanisms and correlations with clinical severity. Epilepsia, 2013, 54(Suppl 3):192.
17. Catterall WA. From ionic currents to molecular mechanisms:the structure and function of voltage-gated sodium channels. Neuron, 2000, 26(10):13-25.

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