Xenbase is experiencing difficulties due to technical problems with the University of Calgary IT infrastructure and may go temporarily offline.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-654
Nat Genet. April 1, 2006; 38 (4): 447-51.

Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes.

Waters MF , Minassian NA , Stevanin G , Figueroa KP , Bannister JP , Nolte D , Mock AF , Evidente VG , Fee DB , Müller U , Dürr A , Brice A , Papazian DM , Pulst SM .


Abstract
Potassium channel mutations have been described in episodic neurological diseases. We report that K+ channel mutations cause disease phenotypes with neurodevelopmental and neurodegenerative features. In a Filipino adult-onset ataxia pedigree, the causative gene maps to 19q13, overlapping the SCA13 disease locus described in a French pedigree with childhood-onset ataxia and cognitive delay. This region contains KCNC3 (also known as Kv3.3), encoding a voltage-gated Shaw channel with enriched cerebellar expression. Sequencing revealed two missense mutations, both of which alter KCNC3 function in Xenopus laevis expression systems. KCNC3(R420H), located in the voltage-sensing domain, had no channel activity when expressed alone and had a dominant-negative effect when co-expressed with the wild-type channel. KCNC3(F448L) shifted the activation curve in the negative direction and slowed channel closing. Thus, KCNC3(R420H) and KCNC3(F448L) are expected to change the output characteristics of fast-spiking cerebellar neurons, in which KCNC channels confer capacity for high-frequency firing. Our results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases.

PubMed ID: 16501573
Article link: Nat Genet.
Grant support: R01GM43459 NIGMS NIH HHS , R01GM66686 NIGMS NIH HHS , R01N533123 PHS HHS , T32GM065823 NIGMS NIH HHS , R01 GM043459-16 NIGMS NIH HHS , R01 GM043459-17 NIGMS NIH HHS , R01 GM043459 NIGMS NIH HHS

Genes referenced: kcnc3


My Xenbase: [ Log-in / Register ]
version: [3.11.2]

Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556