Abstracts

RATIONALE: We report a large multigenerational French family with a homogeneous phenotype consisting of isolated simple Febrile Seizures (FS). The reported loci for FS and Generalised Epilepsy with Febrile Seizures (GEFS+) did not show a linkage to FS trait in our family. A new locus for FS (FEB5) was identified through a genome wide search.
METHODS: Clinical study: Our family consisted of 166 individuals on 5 generations. Twenty-eight presented a history of simple FS that segregates as autosomic dominant trait. We collected 40 blood samples, 18 of them from affected family members. Information concerning each sibship was obtained from the mothers for a more reliable account of FS. All medical records of affected individuals were also reviewed.
Genotyping and linkage analysis: Family members were genotyped with 4 to 6 satellite markers for each locus reported in FS or GEFS+: FEB1 (8q13-q21), FEB2 (19p13,3), FEB3 (2q23-q24), FEB4 (5q14-q15), GEFS+1 (19q13,1), GEFS+2 (2q21-q33). A genome wide search was performed with 380 markers.
RESULTS: All affected individuals presented at least 2 FS except one individual who presented a single FS. All FS were [dsquote]simple[dsquote]. No afebrile seizures or epilepsy were reported following FS. In the oldest generation (II), all individuals were considered having an unknown status since an accurate clinical history from parents was not available.
All known loci for FS and GEFS+ were excluded since they generated load scores [lt]-2 at [theta]= 0,00. The genome wide search allowed the identification of a new candidate region (Zmax=3.31 at [theta]=0.00). Multipoint analysis and haplotypes construction confirmed the genetic linkage of this region to simple FS trait.
CONCLUSIONS: Our family presents a homogeneous phenotype consisting of isolated simple FS, the commonest form of FS. A new locus is identified in this family and the sequence analysis of a potential candidate gene is in progress.