A novel locus for generalized epilepsy with febrile seizures plus in French families.

Abstract : BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a familial autosomal dominant entity characterized by the association of febrile and afebrile seizures. Mutations in 3 genes--the sodium channel alpha1 subunit gene (SCN1A), the sodium channel beta1 subunit gene (SCN1B), and the gamma2 GABA receptor subunit gene (GABRG2)--and linkage to 2 other loci on 2p24 and 21q22 have been identified in families with GEFS(+), indicating genetic heterogeneity. OBJECTIVES: To localize by means of linkage analysis a new gene for GEFS(+) in a large family with 11 affected members and to test the new locus in 4 additional families with GEFS(+). DESIGN: Family-based linkage analysis. SETTING: University hospital. PATIENTS: Five French families with GEFS(+) and at least 7 available affected members with autosomal dominant transmission. All the patients had febrile seizures and/or afebrile generalized tonic-clonic seizures or absence epilepsy. MAIN OUTCOME MEASURES: We analyzed 380 microsatellite markers and conducted linkage analysis. RESULTS: In the largest family, a 10-cM-density genomewide scan revealed linkage to a 13-Mb (megabase) interval on chromosome 8p23-p21 with a maximum pairwise logarithm of odds (LOD) score of 3.00 (at Theta = 0) for markers D8S351 and D8S550 and a multipoint LOD score of 3.23. A second family with GEFS(+) was also possibly linked to chromosome 8p23-p21 and the region was narrowed to a 7.3-Mb candidate interval, flanked by markers D8S1706 and D8S549. We have not, so far, identified mutations in the coding exons of 6 candidate genes (MTMR9, MTMR7, CTSB, SGCZ, SG223, and ATP6V1B2) located in the genetic interval. CONCLUSIONS: We report a sixth locus for GEFS(+) on chromosome 8p23-p21. Because no ion channel genes are located in this interval, identification of the responsible gene will probably uncover a new mechanism of pathogenesis for GEFS(+).
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Archives of Neurology -Chigago-, American Medical Association, 2008, pp.65(7):943-51
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Soumis le : lundi 28 juillet 2008 - 14:43:17
Dernière modification le : mercredi 21 mars 2018 - 18:57:25
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  • HAL Id : inserm-00306473, version 1
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Stéphanie Baulac, Isabelle Gourfinkel-An, Philippe Couarch, Christel Depienne, Anna Kaminska, et al.. A novel locus for generalized epilepsy with febrile seizures plus in French families.. Archives of Neurology -Chigago-, American Medical Association, 2008, pp.65(7):943-51. 〈inserm-00306473〉

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