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

Hum Genet. 2006 Jan;118(5):618-25. doi: 10.1007/s00439-005-0077-x. Epub 2005 Nov 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5*
  • Epilepsy / genetics*
  • Female
  • Genetic Linkage*
  • Genome, Human*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Receptors, G-Protein-Coupled / genetics*
  • Seizures, Febrile / genetics*


  • ADGRV1 protein, human
  • Receptors, G-Protein-Coupled