Abstract
Febrile seizures (FS) are common in children, and the incidence is 2–5% before the age of 5 years. A four-generation Chinese family with autosomal dominant febrile seizure and epilepsy was studied by genome-wide linkage analysis. Significant linkage was identified with markers on chromosome 3q26.2–26.33 with a maximum pairwise LOD score of >3.00. Fine mapping defined the new genetic locus within a 10.7-Mb region between markers D3S3656 and D3S1232. A maximum multipoint LOD score of 5.27 was detected at marker D3S1565. A previously reported CLCN2 gene for epilepsy was excluded as the disease-causing gene in the family by mutational analysis of all exons and exon–intron boundaries of CLCN2 and by haplotype analysis. Mutation analysis of KCNMB2 and KCNMB3, which were two potassium-channel genes in this linkage region, did not reveal a disease causing mutation. Our results identified another novel locus on chromosome 3q26.2–26.33, and future studies of the candidate genes at the locus will identify a new gene for combined FS and idiopathic epilepsies.
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Acknowledgments
We thank all members of the families for their support of this research. This study would be impossible without their enthusiastic participation. This work was supported by the Chinese National Natural Science Foundation grants (No. 30670736, to J.Y.L.), and the Chinese Ministry of Science and Technology National High Technology “863” Programs of China No. 2006AA02Z476 and the National Basic Research Program of China (973 Program) 2007CB512001 and 2007CB512002 (Q.K.W.).
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X.-H. Dai, W.-W. Chen, and X. Wang contributed equally to this work.
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Dai, XH., Chen, WW., Wang, X. et al. A novel genetic locus for familial febrile seizures and epilepsy on chromosome 3q26.2–q26.33. Hum Genet 124, 423–429 (2008). https://doi.org/10.1007/s00439-008-0566-9
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DOI: https://doi.org/10.1007/s00439-008-0566-9