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Human Molecular Genetics, 2000, Vol. 9, No. 1 87-91
© 2000 Oxford University Press

Significant evidence for linkage of febrile seizures to chromosome 5q14–q15

Junko Nakayama1,2, Kenzo Hamano3, Nobuaki Iwasaki2, Satoko Nakahara4, Yumi Horigome2, Hisako Saitoh2, Takeshi Aoki2, Takako Maki2, Masahiro Kikuchi5, Takuo Migita6, Tatsuyuki Ohto2, Yukako Yokouchi2, Ryuta Tanaka2, Makoto Hasegawa2, Akira Matsui2, Hideo Hamaguchi1 and Tadao Arinami1,+

1Department of Medical Genetics, Institute of Basic Medical Sciences and 2Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan, 3Department of Pediatrics, Kitaibaraki Municipal General Hospital, Ibaraki 319-1702, Japan, 4Department of Pediatrics, Kensei General Hospital, Ibaraki 309-1223, Japan, 5Department of Pediatrics, Hitachi General Hospital, Ibaraki 317-0077, Japan and 6Department of Pediatrics, Tsukuba Memorial Hospital, Ibaraki 300-2622, Japan

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13–q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na+)-channel ß1 subunit gene (SCN1B) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS+). These loci are linked to some large families. In this study, we conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER (P = 5.4 x 10–6). Estimated {lambda}s at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14–q15 that confers susceptibility to FSs and we call this gene FEB4.

+ To whom correspondence should be addressed. Tel: +81 298 53 3352; Fax: +81 298 53 3177; Email: tarinami@md.tsukuba.ac.jp


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