Molecular Genetics of Febrile Seizures

• Published in: Epilepsia (Copenhagen) 2002-01, Vol.43 (s9), p.32-35
• Main Authors: Iwasaki, Nobuaki, Nakayama, Junko, Hamano, Kenzo, Matsui, Akira, Arinami, Tadao
• Format: Article
• Language: English
• Subjects: Age Factors; Biological and medical sciences; Child, Preschool; Chromosome Aberrations; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Chromosomes, Human, Pair 2 - genetics; Chromosomes, Human, Pair 5 - genetics; Chromosomes, Human, Pair 8 - genetics; Diseases in Twins - genetics; Epilepsy, Generalized - diagnosis; Epilepsy, Generalized - genetics; Febrile convulsion; Generalized epilepsy with febrile seizures plus (GEFS+); Genes, Dominant; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Linkage analysis; Lod Score; Medical sciences; Models, Genetic; Molecular Biology; Molecular genetics; Nervous system (semeiology, syndromes); Neurology; Pedigree; Seizures, Febrile - diagnosis; Seizures, Febrile - genetics; Seizures, Febrile - metabolism; Sodium Channels - genetics; Sodium Channels - metabolism
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1046/j.1528-1157.43.s.9.8.x

Febrile seizures are the most common form of convulsion, occurring in 2–5% of infants in Europe and North America and in 6–9% in Japan. In large families, the febrile seizure (FS) susceptibility trait is inherited by the autosomal dominant pattern with reduced penetrance. Two putative FS loci, FEB1 (chromosome 8q13‐q21) and FEB2 (chromosome 19p13.3) have been mapped. A clinical subset of FS, termed generalized epilepsy with febrile seizures plus (GEFS+), was reported. In GEFS+ families, a mutation in the voltage‐gated sodium channel β1 subunit gene (SCN1B) at chromosome 19q13.1 and two mutations of the same α1 subunit gene (SCN1A) at chromosome 2q24 were identified. These loci are linked to febrile convulsions in large families. We conducted a genome‐wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families using nonparametric allele‐sharing methods, and found a new FS susceptibility locus, FEB4 (chromosome 5q14‐q15). In contrast to the FEB1, FEB2, and GEFS+ genetic loci, linkage to FEB4 was suggested in nuclear FS families, indicating that FEB4 may be the most common linkage locus in FS families.