title: Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation.
abstract: Febrile seizures (FS) represent the most common seizure disorder in childhood and contribution of a genetic predisposition has been clearly proven. In some families FS is associated with a wide variety of afebrile seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS, atypical febrile seizures (FS+) and afebrile generalized and partial seizures. Mutations in the genes SCN1B, SCN1A and GABRG2 were identified in GEFS+ families. GEFS+ is genetically heterogeneous and mutations in these three genes were detected in only a minority of the families. We performed a 10 cM density genome-wide scan in a multigenerational family with febrile seizures and epilepsy and obtained a maximal multipoint LOD score of 3.12 with markers on chromosome 5q14.3-q23.1. Fine mapping and segregation analysis defined a genetic interval of approximately 33 cM between D5S2103 and D5S1975. This candidate region overlapped with a previously reported locus for febrile seizures (FEB4) in the Japanese population, in which MASS1 was proposed as disease gene. Mutation analysis of the exons and exon-intron boundaries of MASS1 in our family did not reveal a disease causing mutation. Our linkage data confirm for the first time that a locus on chromosome 5q14-q23 plays a role in idiopathic epilepsies. However, our mutation data is negative and do not support a role for MASS1 suggesting that another gene within or near the FEB4 locus might exist.
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics VIB8, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerpen, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Deprez
authors.forename: Lieve R F
authors.initials: LR
authors.lastname: Claes
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Dominique
authors.initials: D
authors.lastname: Audenaert
authors.forename: Tine
authors.initials: T
authors.lastname: Van Dyck
authors.forename: Dirk
authors.initials: D
authors.lastname: Goossens
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: C417525:ADGRV1 protein, human; D043562:Receptors, G-Protein-Coupled