Publication: Identification and functional characterization of a novel homozygous mutation in KCNMA1 encoding voltage and calcium sensitive potassium channel is associated with dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy
dc.contributor.author | Servet Göncü, Beyza | |
dc.contributor.author | Aslanger, Ayça Dilruba | |
dc.contributor.author | Özgül, Cemil | |
dc.contributor.author | Hasanoğlu, Sevde | |
dc.contributor.author | Yeşil Sayın, Gözde | |
dc.contributor.institutionauthor | YÜCESAN, EMRAH | |
dc.contributor.institutionauthor | GÖNCÜ, BEYZA SERVET | |
dc.date.accessioned | 2021-02-09T20:59:35Z | |
dc.date.available | 2021-02-09T20:59:35Z | |
dc.date.issued | 2020-12-01T00:00:00Z | |
dc.description.abstract | Introduction: KCNMA1 encodes, the alpha subunit of the voltage, and calcium-sensitive potassium channel, predominantly expressed in the central nervous system. Therefore abnormal function in this gene may occur neurological conditions.Materials and Methods: We report 15-year-old patient who was born at term with healthy conditions. Motor signals were delayed, and also seizures started at the age of 18 months. EEG revealed generalized spike-wave activities. Brain MRI performed, atrophy of the cerebellum was detected. Recent clinical examination; contractures on the large joints, and dyskinetic tremor. Whole exome sequencing (WES) was performed and in-slico analyses were conducted. MCF7 and 293T cells transfected with either wild-type or mutant expression vectors. Cellular distribution was determined by immunofluorescence. Functional analysis was performed using electrophysiological approach based on whole-cell patch-clamp.Results: WES revealed homozygous variation (NM_001161352.1:c.1372C>T, p.Arg458Ter). The variant was not observed in publicly available or in-house databases. Immunofluorescent staining revealed that novel variant is not interfering with the synthesis of KCNMA1 however mutation exhibit dominant-negative effect on cell viability when compared to wild-type. 293T and MCF7 cells transfected with homozygous p.Arg458Ter mutation showed markedly increased KCNMA1 currents compared to controls on patch-clamp recording, and these data support loss-of-function effect of all KCNMA1 mutants.Conclusions: Herein we report a 15-year old boy who has neurological conditions. A novel homozygous stop-gain mutation detected by WES and confirmed by conventional sequencing. Afterward, functional characterization was conducted using two step-approach, immunostaining to detect subcellular effect of the variation and patch-clamp to detect a difference between mutant vs. wild-type of the protein. Homozygous mutation was considered as causative for this clinical condition. This study was supported by Bezmialem Vakif University, Scientific Research Projects Unit, Project No:2.2019/7. | |
dc.identifier.uri | http://hdl.handle.net/20.500.12645/28404 | |
dc.subject | Yücesan E., Servet Göncü B., Aslanger A. D. , Özgül C., Hasanoğlu S., Yeşil Sayın G., -Identification and functional characterization of a novel homozygous mutation in KCNMA1 encoding voltage and calcium sensitive potassium channel is associated with dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy-, Conference of the European-Society-of-Human-Genetics (ESHG), 6 - 09 Eylül 2020, cilt.28, ss.204-205 | |
dc.title | Identification and functional characterization of a novel homozygous mutation in KCNMA1 encoding voltage and calcium sensitive potassium channel is associated with dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy | |
dc.type | Conference Paper | |
dspace.entity.type | Publication | |
local.avesis.id | e94c1b98-baea-4475-bd19-d6b1d34de9fc | |
local.publication.isinternational | 1 | |
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