MUTATIONS OF THE SODIUM CHANNEL [alpha]1 SUBUNIT GENE IN JAPANESE PATIENTS WITH SEVERE MYOCLONIC EPILEPSY IN INFANCY (SMEI)
Abstract number :
D.02
Submission category :
Year :
2002
Submission ID :
2181
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Goryu Fukuma, Shinichi Hirose, Akihisa Mitsudome. Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Fukuoka, Japan
RATIONALE: To identify genetic abnormalities underlying severe myoclonic epilepsy in infancy (SMEI) in Japanese. Recently, mutations of the neuronal voltage-gated Na+ channel [alpha]1 subunit gene ([italic]SCN1A[/italic]) and [gamma]-aminobutyric acid (GABA)[sub]A[/sub] receptor [gamma]2 subunit gene ([italic]GABRG2[/italic]) have been identified as a cause of SMEI. [italic]SCN1A[/italic] and genes encoding other components of Na+ channels in the brain such as [alpha]2, [beta]1 and [beta]2 subunits ([italic]SCN2A[/italic], [italic]SCN1B[/italic] and [italic]SCN2B[/italic], respectively) and [italic]GABRG2[/italic] can be candidate genes for SMEI.
METHODS: Our study recruited 54 unrelated individuals whose clinical manifestations were consistent with SMEI and 96 healthy volunteers. Each participant or a responsible person signed an informed consent form approved by the Ethics Review Committee of Fukuoka University or similar committees of the participating institutions. Genetic abnormalities of [italic]SCN1A[/italic], [italic]SCN2A[/italic], [italic]SCN1B[/italic], [italic]SCN2B[/italic] and [italic]GABRG2[/italic] were sought in genomic DNA using a direct sequencing method with an ABI 3700 sequencer.
RESULTS: In [italic]SCN1A[/italic], eight heterozygous nonsense, 23 missense and three frame-shift mutations resulting in a premature stop were found in 44 individuals with SMEI. The mutations identified in the patients were not found in 96 healthy volunteers and hence considered to be disease causing mutations. No mutation was found within the examined region of [italic]SCN2A[/italic], [italic]SCN1B[/italic], [italic]SCN2B[/italic] and [italic]GABRG2[/italic].
CONCLUSIONS: In the first report made by Claes et al. , mutations of [italic]SCN1A[/italic] were found in all patients they studied while only 44 of 54 patients bore causative mutations in [italic]SCN1A[/italic] in our subjects. The relation between phenotype and genotype of SMEI should be further delineated.
[Supported by: The Ministry of Education, Culture, Sports, Science, and Technology of Japan, The Epilepsy Research Foundation, The Clinical Research Foundation, The Foundation for the Advancement of Clinical Medicine, and The Central Research Institute of Fukuoka University Ministry of Education Science and Culture of Japan.]