Novel KCNQ3 muation in a large family with benign familial neonatal epilepsy: a rare cause of neonatal seizures
Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by <i>KCNQ2</i> and <i>KCNQ3.</i> While most BFNS families carry alterations in <i>KCNQ2<...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 7, 2016
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| In: |
Molecular syndromology
Year: 2016, Volume: 7, Issue: 4, Pages: 189-196 |
| ISSN: | 1661-8777 |
| DOI: | 10.1159/000447461 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000447461 Verlag, lizenzpflichtig, Volltext: https://www.karger.com/Article/FullText/447461 
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| Author Notes: | Snezana Maljevic, Sabina Vejzovic, Matthias K. Bernhard, Astrid Bertsche, Sebastian Weise, Miriam Döcker, Holger Lerche, Johannes R. Lemke, Andreas Merkenschlager, Steffen Syrbe |
| Summary: | Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by <i>KCNQ2</i> and <i>KCNQ3.</i> While most BFNS families carry alterations in <i>KCNQ2</i>, mutations in <i>KCNQ3</i> appear to be less common. Here, we describe a family with 6 individuals presenting with neonatal focal and generalized seizures. Genetic testing revealed a novel <i>KCNQ3</i> variant, c.835G>T, cosegregating with seizures in 4 tested individuals. This variant results in a substitution of the highly conserved amino acid valine localized within the pore-forming transmembrane segment S5 (p.V279F). Functional investigations in <i>Xenopus laevis</i> oocytes revealed a loss of function, which supports p.V279F as a pathogenic mutation. When p.V279F was coexpressed with the wild-type (WT) Kv7.2 subunits, the resulting potassium currents were about 10-fold reduced compared to the WT Kv7.3 and Kv7.2 coexpression. Genotype-phenotype correlation shows an incomplete penetrance of p.V279F. Response to antiepileptic treatment was variable, but evaluation of treatment response remained challenging due to the self-limiting character of the disease. The identification of the pathogenic variant helped to avoid unnecessary investigations in affected family members and allowed guided therapy. |
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| Item Description: | Gesehen am 06.05.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1661-8777 |
| DOI: | 10.1159/000447461 |