PMID- 10355668
OWN - NLM
STAT- MEDLINE
DCOM- 19990615
LR  - 20190513
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 122 ( Pt 5)
DP  - 1999 May
TI  - A novel mutation in the human voltage-gated potassium channel gene (Kv1.1)
      associates with episodic ataxia type 1 and sometimes with partial epilepsy.
PG  - 817-25
AB  - Episodic ataxia type 1 (EA1) is a rare autosomal dominant disorder characterized 
      by brief episodes of ataxia associated with continuous interattack myokymia.
      Point mutations in the human voltage-gated potassium channel (Kv1.1) gene on
      chromosome 12p13 have recently been shown to associate with EA1. A Scottish
      family with EA1 harbouring a novel mutation in this gene is reported. Of the five
      affected individuals over three generations, two had partial epilepsy in addition
      to EA1. The detailed clinical, electrophysiological and molecular genetic
      findings are presented. The heterozygous point mutation is located at nucleotide 
      position 677 and results in a radical amino acid substitution at a highly
      conserved position in the second transmembrane domain of the potassium channel.
      Functional studies indicated that mutant subunits exhibited a dominant negative
      effect on potassium channel function and would be predicted to impair neuronal
      repolarization. Potassium channels determine the excitability of neurons and
      blocking drugs are proconvulsant. A critical review of previously reported EA1
      families shows an over-representation of epilepsy in family members with EA1
      compared with unaffected members. These observations indicate that this mutation 
      is pathogenic and suggest that the epilepsy in EA1 may be caused by the
      dysfunctional potassium channel. It is possible that such dysfunction may be
      relevant to other epilepsies in man.
FAU - Zuberi, S M
AU  - Zuberi SM
AD  - Department of Neurology and Child Development, Royal Hospital for Sick Children, 
      Glasgow, UK.
FAU - Eunson, L H
AU  - Eunson LH
FAU - Spauschus, A
AU  - Spauschus A
FAU - De Silva, R
AU  - De Silva R
FAU - Tolmie, J
AU  - Tolmie J
FAU - Wood, N W
AU  - Wood NW
FAU - McWilliam, R C
AU  - McWilliam RC
FAU - Stephenson, J B
AU  - Stephenson JB
FAU - Kullmann, D M
AU  - Kullmann DM
FAU - Hanna, M G
AU  - Hanna MG
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (KCNA1 protein, human)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 147173-20-4 (Kv1.1 Potassium Channel)
SB  - IM
EIN - Brain. 2007 Mar;130(Pt 3):879. Stephenson, J P [corrected to Stephenson, J B]
EIN - Brain. 2010 May;133(Pt 5):1569
MH  - Adult
MH  - Ataxia/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Electroencephalography
MH  - Electromyography
MH  - Epilepsies, Partial/*genetics
MH  - Female
MH  - Humans
MH  - *Ion Channel Gating
MH  - Kv1.1 Potassium Channel
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Middle Aged
MH  - Mutation
MH  - Pedigree
MH  - *Periodicity
MH  - Polymerase Chain Reaction
MH  - Potassium Channels/*genetics
MH  - *Potassium Channels, Voltage-Gated
EDAT- 1999/06/04 00:00
MHDA- 1999/06/04 00:01
CRDT- 1999/06/04 00:00
PHST- 1999/06/04 00:00 [pubmed]
PHST- 1999/06/04 00:01 [medline]
PHST- 1999/06/04 00:00 [entrez]
AID - 10.1093/brain/122.5.817 [doi]
PST - ppublish
SO  - Brain. 1999 May;122 ( Pt 5):817-25. doi: 10.1093/brain/122.5.817.