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Febrile seizures are associated with mutation of seizure-related (SEZ) 6, a brain-specific gene

Authors

  • Zhi-liang Yu,

    Corresponding author
    1. Department of Neurology, No. 3 People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    2. Department of Neurology, Changhai Hospital, Second Military Medical University of PLA, Shanghai, China
    • Department of Neurology, No. 3 People's Hospital, School of Medicine, Shanghai Jiao Tong University; No 50 Mo-he Road, Bao-shan District, Shanghai 201900, P.R. China
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    • Zhi-liang Yu and Jiang-ming Jiang contributed equally to this article.

  • Jiang-ming Jiang,

    1. Department of Neurology, Changhai Hospital, Second Military Medical University of PLA, Shanghai, China
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    • Zhi-liang Yu and Jiang-ming Jiang contributed equally to this article.

  • Dan-hong Wu,

    1. Department of Neurology, No. 3 People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Hui-jun Xie,

    1. Department of Neurology, Changhai Hospital, Second Military Medical University of PLA, Shanghai, China
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  • Jin-jin Jiang,

    1. Department of Pediatrics, Changhai Hospital, Second Military Medical University of PLA, Shanghai, China
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  • Lin Zhou,

    1. Department of Pediatrics, Changhai Hospital, Second Military Medical University of PLA, Shanghai, China
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  • Ling Peng,

    1. International Joint Cancer Institute, Second Military Medical University of PLA, Shanghai, China
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  • Guan-shui Bao

    1. Department of Neurology, No. 3 People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Abstract

Genetic factors contribute significantly to the etiology of febrile seizures (FS), the most common type of seizures in childhood. However, in most patients with FS, the causative gene is unknown. The purpose of this study was to explore the relationship between human brain-specific gene SEZ-6 and FS. Through amplification of genomic DNA by PCR and sequencing of the resulting products, we screened 75 subjects for mutations in the coding region (17 exons) of the SEZ-6 gene. Fifteen subjects were healthy individuals and 60 subjects had FS. Patients with FS could be divided into sub-groups based on seizure type (42 simple and 18 complex) and family history (41 had a positive family history). All patients have been followed to date to evaluate seizure recurrence and the development of epilepsy. No mutations were found in healthy controls, but 21 of the patients with FS had mutations in SEZ-6, and the most common type of mutation was a heterozygous, cytosine insertion (frame shift mutation) at position 1435 of the cDNA. The mutation incidence was significantly higher in patients with complex FS (vs. simple FS) and in patients with a positive family history. Sixteen of 42 patients with simple FS experienced seizure recurrence during the 1–5-year follow-up period. Fifteen of 18 patients with complex FS also experienced a recurrence during this period. Among these patients with recurrences, five patients with simple FS and six patients with complex FS have developed epilepsy. The mutation incidence among these epileptic patients is 72.7%. The human SEZ-6 gene is related to the occurrence and development of FS and may be a novel candidate gene for epilepsy. Screening for mutations in SEZ-6 may be valuable in predicting FS recurrence or the development of epilepsy. © 2006 Wiley-Liss, Inc.

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