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Arch Neurol. 2008 Jul;65(7):943-51. doi: 10.1001/archneur.65.7.943.

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

Author information

1
INSERM, UMR679, Neurologie and Thérapeutique Expérimentale, UPMC Univ Paris 06, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l'hôpital, 75013 Paris, France. baulac@ccr.jussieu.fr

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(+).

PMID:
18625863
DOI:
10.1001/archneur.65.7.943
[Indexed for MEDLINE]
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