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Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation

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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 ≈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.

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Acknowledgements

The authors are grateful to the patients and their family members for their cooperation and participation in this study. We acknowledge the contribution of the VIB Genetic Service Facility (http://www.vibgeneticservicefacility.be) to the genetic analyses. This research was funded by the Fund for Scientific Research Flanders (FWO), University of Antwerp, the Medical Foundation Queen Elisabeth and the Interuniversity Attraction Poles (IUAP) program P5/19 of the Belgian Science Policy Office, Belgium. LD is a PhD fellow of the Institute for Science and Technology and DA of the FWO, Belgium.

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Correspondence to Peter De Jonghe.

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Deprez, L., Claes, L.R.F., Claeys, K.G. et al. Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation. Hum Genet 118, 618–625 (2006). https://doi.org/10.1007/s00439-005-0077-x

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  • DOI: https://doi.org/10.1007/s00439-005-0077-x

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