Characterization of variants in the KCNQ5 gene associated with genetic generalized epilepsy

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Dokumentart: PhDThesis
Date: 2022-04-20
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Lerche, Holger (Prof. Dr.)
Day of Oral Examination: 2022-03-14
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Epilepsy is a common chronic brain disorder of the CNS that affects at least 50 million individuals worldwide and can affect all age groups. It is characterized by recurrent and unpredictable seizures. An increasing number of studies have illustrated that genetic causes could be responsible for idiopathic epilepsy, especially variants in genes encoding ion channels in the cell membrane. Previous studies have already reported that DEEs can be caused by variants in the KCNQ5 gene. Here, I investigated two KCNQ5 variants, p.Val170Ile and p.Arg359Cys, from two GGE families. In my experiment, the whole-cell patch-clamp technique was applied to cells transfected with plasmids expressing a mutant or WT KCNQ5 gene to characterize the functional effects of these two variants. After the analysis of the current traces and the current density of KCNQ5 p.Val170Ile- and p.Arg359Cys-transfected CHO cells, the p.Arg359Cys variant results in a strong loss of function by reducing the current density even under WT co-expression meaning it has a dominant-negative effect. In contrast, the p.Val170Ile variant functions similarly to KCNQ5 WT and might therefore represent a benign polymorphism that is not related to epilepsy in variant carriers.

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