Mutations in KCNT1 cause a spectrum of focal epilepsies.
نویسندگان
چکیده
Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype-phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances.
منابع مشابه
Mesial temporal lobe epilepsy associated with KCNT1 mutation
Several epilepsies such as malignant migrating partial seizures of infancy (MMPSI) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) are caused by mutations in the sodiumactivated potassium channel named KCNT1 [1]. Together with their role in epileptic encephalopathies such as MMPSI, KCNT1 mutations are involved in intellectual disability [1]. This report highlights a new phenotyp...
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ورودعنوان ژورنال:
- Epilepsia
دوره 56 9 شماره
صفحات -
تاریخ انتشار 2015