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| Author(s): |
Marina Coelho Gonsales
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2009-08-18 |
| Examining board members: |
Íscia Teresinha Lopes Cendes;
Maria Luiza Giraldes de Manreza;
Vera Lúcia Gil da Silva Lopes
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| Advisor: | Íscia Teresinha Lopes Cendes |
| Abstract | |
Among the childhood epilepsies one important sub-group is the spectrum of generalized epilepsy with febrile seizures plus (GEFS+), which includes severe syndromes such as severe myoclonic epilepsy of infancy (SMEI) and myoclonic astatic epilepsy (MAE). Another important epileptic syndrome is benign childhood epilepsy with centrotemporal spikes (BCECTS), which is of particular interest for being the most common childhood epilepsy. Advances in molecular genetic studies led to the discovery of the SCN1A gene, responsible for the spectrum of GEFS+, and a candidate locus for BCECTS in the 15q14 region. The main objectives of this project were to screen candidate genes for mutations in a cohort of patients diagnosed with the epilepsies mentioned above, and to established genotype-phenotype correlations. We studied the SCN1A gene in patients with SMEI and MAE; and CHRM5, CHRNA7, and CX36 genes, located within the candidate region on chromosome 15q14, in patients with BCECTS. Mutation screening was performed using the denaturing high performance liquid chromatography (DHPLC) technique, with subsequent automatic sequencing of the altered fragments. We investigated 9 patients with SMEI, 12 with MAE and 27 with BCECTS. Analysis of the SCN1A gene revealed 6 potentially deleterious variants: substitutions c.829T>C, c.971A>C and c.5434T>C, leading to amino acid residue substitutions; insertion c.3719_3720insGATA, which promotes a frameshift; and alterations IVS4+1G>A and IVS8+3G>T, which possibly modify splicing donor sites. We found alterations only in patients with the most severe phenotype, SMEI, who had seizures during low temperature fever occur. Mutation analysis in patients diagnosed with BCECTS did not reveal potentially deleterious variants for the genes studied. As a result of our study, we can conclude that we only found potentially deleterious variants in the SCN1A gene among the patients studied. The fact that they were identified only in patients with SMEI provides evidence that another gene is likely to be involved in the etiology of MAE. The CHRM5 gene does not seem to be involved in the etiology of BCECTS in our patients. Even though no evidences supporting the pathologic role of CHRNA7 and CX36 genes were found, we still can not exclude them as involved in BCECTS. (AU) | |