First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy
作者： Katrien Smets , Anna Duarri , Tine Deconinck , Berten Ceulemans , Bart P van de Warrenburg
DOI: 10.1186/S12881-015-0200-3
关键词: Epilepsy 、 Genetics 、 Spinocerebellar ataxia 、 Spinocerebellar Degenerations 、 Apraxia 、 Myokymia 、 Channelopathy 、 Pathology 、 Biology 、 Cerebellar ataxia 、 Exome sequencing
摘要: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) a patient with complex early onset cerebellar ataxia order to expand genetic and phenotypic spectrum. Whole exome sequencing subsequent immunocytochemistry, immunoblotting patch clamp assays channel were performed. A KCND3 (c.877_885dupCGCGTCTTC; p.Arg293_Phe295dup) was found duplicating RVF motif thereby adding an extra positive charge 4.3 (Kv4.3) voltage-sensor domain causing severe shift voltage-dependence gating more depolarized voltages. The displayed phenotype complicated by intellectual disability, epilepsy, attention deficit hyperactivity disorder, strabismus, oral apraxia joint hyperlaxity. We identified most marked change Kv4.3’s properties reported so far, which correlated unique spinocerebellar (SCA) type 19/22 disease phenotype.
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