Association Analysis of γ2 Subunit of γ-aminobutyric Acid (GABA) Type A Receptor and Voltage-gated Sodium Channel Type II α-polypeptide Gene Mutation in Southern Chinese Children With Febrile Seizures

Abstract

We attempted to identify the prevalence of the R188W mutation of the SCN2A gene and the K289M mutation and single-nucleotide polymorphism rs211014 of the GABRG2 gene in children of southern China who have febrile seizures. Neither mutation was found in our subjects. The single-nucleotide polymorphism rs211014 AA genotype was overrepresented in the febrile-seizures group compared with controls (62.4% vs 29.0%). The single-nucleotide polymorphism rs211014 A allele was higher in the febrile-seizures group (P < .005). Compared with the single-nucleotide polymorphism rs211014 CC genotype, the odds ratio for developing febrile seizures in individuals with the single-nucleotide polymorphism rs211014 AA genotype was 4.05 (P < .005). A new mutation of C-to-T transition was found at nucleotide 81719 of the GABRG2 gene in a 5-year-old boy, suggesting that the above mutations may not be the main disease mutations. The single-nucleotide polymorphism rs211014 A allele may predict susceptibility to febrile seizures.

Keywords

gene mutation familial febrile seizures single nucleotide polymorphisms GABA

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References

Baumann RJ , Duffner PK Treatment of children with simple febrile seizures: the AAP practice parameter . Pediatr Neurol. 2000;23:11-17.

Vestergaard M. , Basso O. , Henriksen TB , et al. Risk factors for febrile convulsions . Epidemiology. 2002;13:282-287.

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.

Wallace RH , Marini C. , Petrou S. , et al. Mutant GABA [A] receptor gamma-2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet. 2001;28:49-52.

Sugawara T. , Tsurubuchi Y. , Agarwala KL , et al. A missense mutation of the Na+ channel α-II subunit gene Na (v) 1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci U S A. 2001 ;98:6384-6389.

Ito M. , Shirasaka Y. , Hirose S. , et al. Seizure phenotypes of a family with missense mutations in SCN2A . Pediatr Neurol. 2004; 31:150-152.

Rhee JS , Jin YH , Akaike N. Developmental changes of GABA (A) receptor-chloride channels in rat Meynert neurons. Brain Res. 1998;779:9-16.

Ganguly K. , Schinder AF , Wong , ST et al. GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition. Cell. 2001;105:521-532.

Greenfield LJ , Zaman SH , Sutherland ML , et al. Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement . Neuropharmacology. 2002;42:502-521.

10.

Baulac S. , Huberfeld G. , Gourfinkel-An I. , et al. First genetic evidence of GABA (A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001;28:46-48.

11.

Chou IC , Peng CT , Huang CC , et al. Association analysis of gamma 2 subunit of gamma-aminobutyric acid type A receptor polymorphisms with febrile seizures. Pediatr Res. 2003;54:26-29.

12.

Pal DK , Kugler SL , Mandelbaum DE , Durner M. Phenotypic features of familial febrile seizures: case-control study. Neurology. 2003;60:410-414.

13.

Reutens DA , Howell RA , Gebert KE , Berkovic SF Validation of a questionnaire for clinical seizure diagnosis. Epilepsia. 1992;33: 1065-1071.

14.

Heron SE , Crossland KM , Andermann E. , et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet. 2002;360:851-852.

15.

Kullmann DM , Hanna MG Neurological disorders caused by inherited ion-channel mutations. Lancet Neurol. 2002 ;1:157-166.

16.

Maurice N. , Thierry AM , Glowinski J. , Deniau JM Spontaneous and evoked activity of substantia nigra pars reticulata neurons during high-frequency stimulation of the subthalamic nucleus. J Neurosci. 2003;23:9929-9936.

17.

Schmiegelow K. , Johnsen AH , Ebbesen F. , et al. Gamma-aminobutyric acid concentration in lumbar cerebrospinal fluid from patients with febrile convulsions and controls . Acta Paediatr Scand. 1990;79:1092-1098.

18.

Casasola C. , Montiel T. , Calixto E. , Brailowsky S. Hyperexcitability induced by GABA withdrawal facilitates hippocampal long-term potentiation. Neuroscience . 2004;126:163-171.

19.

Yinan M. , Yu Q. , Zhiyue C. , et al. Polymorphisms of casein kinase I gamma 2 gene associated with simple febrile seizures in Chinese Han population. Neurosci Lett. 2004;68:2-6.

20.

Nakayama J. , Yamamoto N. , Hamano K. , et al. Linkage and association of febrile seizures to the IMPA2 gene on human chromosome 18. Neurology . 2004;63:1803-1807.

21.

Simsek M. , Tanira MO , Al-Baloushi KA , et al. Improved detection of the T(341)C polymorphism in human N-acetyltransferase (NAT2) gene by using two complementary PCR-RFLP methods: better than automated DNA sequencing for detection of heterozygotes. Clin Biochem. 2000;33(7):585-588.

22.

Nakayama J. , Yamamoto N. , Hamano K. , et al. Failure to find evidence for association between voltage-gated sodium channel gene SCN2A variants and febrile seizures in humans. Neurosci Lett. 2002;329:249-251.