| Study expanded the genotype-phenotype-pathophysiology repertoire of SCA13 by addition of a causative KCNC3 mutation, p.Pro583_Pro585del, its associated phenotype of profound spasticity, and the decreased inactivation rate of the mutant channel. | C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity.
Khare S, Galeano K, Zhang Y, Nick JA, Nick HS, Subramony SH, Sampson J, Kaczmarek LK, Waters MF., Free PMC Article | 11/10/2018 |
| results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology | A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
Khare S, Nick JA, Zhang Y, Galeano K, Butler B, Khoshbouei H, Rayaprolu S, Hathorn T, Ranum LPW, Smithson L, Golde TE, Paucar M, Morse R, Raff M, Simon J, Nordenskjöld M, Wirdefeldt K, Rincon-Limas DE, Lewis J, Kaczmarek LK, Fernandez-Funez P, Nick HS, Waters MF., Free PMC Article | 09/23/2017 |
| This review covers the localization and physiological function of Kv3.3 in the central nervous system and how the normal function of the channel is altered by the disease-causing mutations | Kv3.3 potassium channels and spinocerebellar ataxia.
Zhang Y, Kaczmarek LK., Free PMC Article | 09/2/2017 |
| Kv3.3 regulates Arp2/3-dependent cortical actin nucleation mediated by Hax-1; resulting cortical actin structures interact with the channel's gating machinery to slow its inactivation rate during sustained membrane depolarizations; a mutation that leads to late-onset spinocerebellar ataxia type 13. | Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.
Zhang Y, Zhang XF, Fleming MR, Amiri A, El-Hassar L, Surguchev AA, Hyland C, Jenkins DP, Desai R, Brown MR, Gazula VR, Waters MF, Large CH, Horvath TL, Navaratnam D, Vaccarino FM, Forscher P, Kaczmarek LK., Free PMC Article | 09/3/2016 |
| The Kv channels, or at least Kv3.3, appear to be associated with cell differentiation | Voltage-Gated K+ Channel, Kv3.3 Is Involved in Hemin-Induced K562 Differentiation.
Song MS, Choi SY, Ryu PD, Lee SY., Free PMC Article | 07/16/2016 |
| Functional and in silico analysis identified at least one novel pathogenic mutation in KCNC3 that cause Spinocerebellar ataxia type 13 (SCA13) and two additionally potential ones. | Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases.
Duarri A, Nibbeling EA, Fokkens MR, Meijer M, Boerrigter M, Verschuuren-Bemelmans CC, Kremer BP, van de Warrenburg BP, Dooijes D, Boddeke E, Sinke RJ, Verbeek DS., Free PMC Article | 01/16/2016 |
| investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2 | De novo point mutations in patients diagnosed with ataxic cerebral palsy.
Parolin Schnekenberg R, Perkins EM, Miller JW, Davies WI, D'Adamo MC, Pessia M, Fawcett KA, Sims D, Gillard E, Hudspith K, Skehel P, Williams J, O'Regan M, Jayawant S, Jefferson R, Hughes S, Lustenberger A, Ragoussis J, Jackson M, Tucker SJ, Németh AH., Free PMC Article | 09/12/2015 |
| These results are specific to the KCNC3(R420H) allele and provide new insight into the molecular basis of disease manifestation in SCA13. | KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking.
Gallego-Iradi C, Bickford JS, Khare S, Hall A, Nick JA, Salmasinia D, Wawrowsky K, Bannykh S, Huynh DP, Rincon-Limas DE, Pulst SM, Nick HS, Fernandez-Funez P, Waters MF., Free PMC Article | 06/6/2015 |
| Data indicate that an autosomal dominant mutation in the gene encoding Kv3.3 has been identified in a large Filipino kindred manifesting as spinocerebellar ataxia type 13 (SCA13). | Mutation in the kv3.3 voltage-gated potassium channel causing spinocerebellar ataxia 13 disrupts sound-localization mechanisms.
Middlebrooks JC, Nick HS, Subramony SH, Advincula J, Rosales RL, Lee LV, Ashizawa T, Waters MF., Free PMC Article | 08/9/2014 |
| no disease-related KCNC3 mutation was identified, suggesting that spinocerebellar ataxia type 13 is a rare form of SCA in mainland China | Spinocerebellar ataxia type 13 is an uncommon SCA subtype in the Chinese Han population.
Peng L, Wang C, Chen Z, Wang JL, Tang BS, Jiang H. | 06/28/2014 |
| This study presented the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis. | Comprehensive phenotype of the p.Arg420his allelic form of spinocerebellar ataxia type 13.
Subramony SH, Advincula J, Perlman S, Rosales RL, Lee LV, Ashizawa T, Waters MF., Free PMC Article | 05/31/2014 |
| Data suggest that mutant forms of Kv3.3 (as seem in subjects with spinocerebellar ataxia-13) are unstable, are degraded through proteasomes at faster rates, and can be stabilized by a chemical chaperone. | Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine mutations affect both functional and protein expression on the cell surface.
Zhao J, Zhu J, Thornhill WB. | 11/16/2013 |
| Kv3.3 gating contributes significantly to an early age of onset in spinocerebellar ataxia type 13 | Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13.
Minassian NA, Lin MC, Papazian DM., Free PMC Article | 08/11/2012 |
| The KCNC3 mutation casued Spinocerebellar ataxia 13. | Spinocerebellar ataxia 13 and 25.
Stevanin G, Dürr A. | 12/10/2011 |
| The spinocerebellar ataxia type 13 mutation of the KV3.3 gene specifically suppresses the excitability of Kv3.3-expressing, fast-spiking neurons in zebrafish | Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish.
Issa FA, Mazzochi C, Mock AF, Papazian DM., Free PMC Article | 08/6/2011 |
| Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. | Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13).
Figueroa KP, Waters MF, Garibyan V, Bird TD, Gomez CM, Ranum LP, Minassian NA, Papazian DM, Pulst SM., Free PMC Article | 07/30/2011 |
| The p.Arg420His mutation, which results in a nonfunctional channel subunit, was recurrent and associated with late-onset progressive ataxia. | KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients.
Figueroa KP, Minassian NA, Stevanin G, Waters M, Garibyan V, Forlani S, Strzelczyk A, Bürk K, Brice A, Dürr A, Papazian DM, Pulst SM., Free PMC Article | 05/3/2010 |
| Mutations in the voltage-gated potassium channel KCNC3 are causative for spinocerebellar ataxia 13. | Sca13.
Waters MF, Pulst SM. | 01/21/2010 |
| Observational study of genotype prevalence. (HuGE Navigator) | Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families.
Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, Fetoni V, Mariotti C, Migone N, Di Donato S, Taroni F. | 03/13/2008 |
| 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 | 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. | 01/21/2010 |