Functional analysis helps to define KCNC3 mutational spectrum in dutch ataxia cases

PloS One
Anna DuarriDineke S Verbeek

Abstract

Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominantly inherited neurodegenerative disorder of the cerebellum caused by mutations in the voltage gated potassium channel KCNC3. To identify novel pathogenic SCA13 mutations in KCNC3 and to gain insights into the disease prevalence in the Netherlands, we sequenced the entire coding region of KCNC3 in 848 Dutch cerebellar ataxia patients with familial or sporadic origin. We evaluated the pathogenicity of the identified variants by co-segregation analysis and in silico prediction followed by biochemical and electrophysiological studies. We identified 19 variants in KCNC3 including 2 non-coding, 11 missense and 6 synonymous variants. Two missense variants did not co-segregate with the disease and were excluded as potentially disease-causing mutations. We also identified the previously reported p.R420H and p.R423H mutations in our cohort. Of the remaining 7 missense variants, functional analysis revealed that 2 missense variants shifted Kv3.3 channel activation to more negative voltages. These variations were associated with early disease onset and mild intellectual disability. Additionally, one other missense variant shifted channel activation to more positive voltages and ...Continue Reading

References

Aug 17, 2001·Trends in Neurosciences·B Rudy, C J McBain
Dec 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qingwei DengRobert J Dunn
Aug 23, 2006·Genes, Brain, and Behavior·R H JohoT Knöpfel
Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Sanjeev RajakulendranMichael G Hanna
Apr 21, 2007·The Journal of Comparative Neurology·Su Ying ChangBernardo Rudy
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Edward ZaghaBernardo Rudy
Feb 28, 2009·The Cerebellum·Rolf H Joho, Edward C Hurlock
Dec 3, 2009·Human Mutation·Karla P FigueroaStefan M Pulst
Jul 30, 2010·Journal of Neurology, Neurosurgery, and Psychiatry·Peter BauerAlexis Brice
Apr 12, 2011·PloS One·Karla P FigueroaStefan M Pulst
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fadi A IssaDiane M Papazian
Feb 1, 2012·The Journal of Physiology·Natali A MinassianDiane M Papazian
Oct 31, 2012·Journal of Neurology·Katherine FawcettHenry Houlden
Dec 12, 2012·The International Journal of Neuroscience·Katrin BürkFelix Rosenow
Jan 3, 2013·Annals of Neurology·Anna DuarriDineke S Verbeek
Jan 9, 2013·The International Journal of Neuroscience·Lan PengHong Jiang
Mar 9, 2013·Journal of Neurology·Justyna JezierskaDineke S Verbeek
Dec 7, 2013·Frontiers in Cellular Neuroscience·Ken VeysErik De Schutter

❮ Previous
Next ❯

Citations

Sep 14, 2016·The Journal of General Physiology·David NaranjoIgnacio Díaz-Franulic
Feb 2, 2017·Neuroscience and Biobehavioral Reviews·Esther A R NibbelingDineke S Verbeek
Sep 15, 2017·Physiological Reviews·Leonard K Kaczmarek, Yalan Zhang
Jul 30, 2019·Annals of Clinical and Translational Neurology·Joohyun ParkTobias B Haack
Mar 14, 2019·CNS & Neurological Disorders Drug Targets·Laszlo SzpisjakLaszlo Vecsei
Sep 13, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Justyna Jędrychowska, Vladimir Korzh
Sep 9, 2020·Journal of Movement Disorders·Minkyeong KimJae-Hyeok Lee
Nov 20, 2016·Annals of Neurology·Mahmoud Fawzi ElsaidAlice Abdel Aleem
Jul 14, 2020·Frontiers in Genetics·Miriam KessiFei Yin
Oct 8, 2015·The Journal of Physiology·Yalan Zhang, Leonard K Kaczmarek
Mar 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Meng-Chin A LinDiane M Papazian
Aug 18, 2021·Neurogenetics·Ulrich Müller

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

Mutation Surveyor
PolyPhen2
Align GVGD
Alamut
SigmaPlot
ImageJ
Mutationtaster
SIFT
Clampfit
Softgenetics

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Bovine Spongiform Encephalopathy (MDS)

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Related Papers

Movement Disorders : Official Journal of the Movement Disorder Society
Joyce van de LeemputH Houlden
Handbook of Clinical Neurology
Giovanni Stevanin, Alexandra Durr
Zeitschrift für Neurologie
P E BeckerH C Hopf
© 2022 Meta ULC. All rights reserved