Abstract: Background Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments. Results We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again. Conclusions By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.

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