PMID- 10408533
OWN - NLM
STAT- MEDLINE
DCOM- 19990809
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 53
IP  - 1
DP  - 1999 Jul 13
TI  - A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia.
PG  - 34-7
AB  - OBJECTIVE: To identify the disease-causing mutation and to characterize
      penetrance and phenotypic variability in a large pedigree with episodic ataxia
      type 2 (EA-2) previously linked to chromosome 19. BACKGROUND: Mutations in the
      CACNA1A gene on chromosome 19 encoding a calcium channel subunit cause EA-2,
      which is characterized by recurrent attacks of imbalance with interictal eye
      movement abnormalities. METHODS: The authors used single-strand conformation
      polymorphism (SSCP) analysis to screen for point mutations, and direct sequencing
      to identify mutations in CACNA1A. Allele-specific oligonucleotides were designed 
      to detect the presence of the diseased allele in members of their pedigree as
      well as in normal control subjects. RESULTS: Reassessment of members of the
      pedigree revealed two notable clinical features. Diffuse weakness during attacks 
      of ataxia was a prominent complaint. Two affected individuals had had episodic
      hemiplegia, one with typical migraine headaches. SSCP analysis revealed aberrant 
      bands in exon 29 in affected members but not in normal control subjects. Direct
      sequencing of exon 29 identified a C-to-T change at position 4914 of the coding
      sequence of CACNA1A, predicting an early stop code at codon 1547. Two
      asymptomatic mutation carriers demonstrated the incomplete penetrance of this
      mutation. CONCLUSIONS: A nonsense mutation in CACNA1A causes episodic ataxia and 
      complaint of weakness, and may be associated with hemiplegia.
FAU - Jen, J
AU  - Jen J
AD  - Department of Neurology, University of California at Los Angeles School of
      Medicine, 90095-1769, USA. jjen@ucla.edu
FAU - Yue, Q
AU  - Yue Q
FAU - Nelson, S F
AU  - Nelson SF
FAU - Yu, H
AU  - Yu H
FAU - Litt, M
AU  - Litt M
FAU - Nutt, J
AU  - Nutt J
FAU - Baloh, R W
AU  - Baloh RW
LA  - eng
GR  - AG9063/AG/NIA NIH HHS/United States
GR  - DC00008-21/DC/NIDCD NIH HHS/United States
GR  - P01 DC02952/DC/NIDCD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (CACNA1A protein, human)
RN  - 0 (Calcium Channels)
SB  - IM
CIN - Neurology. 1999 Jul 13;53(1):3-4. PMID: 10408526
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Brain/pathology
MH  - Calcium Channels/*genetics
MH  - Cerebellar Ataxia/*genetics/pathology
MH  - Child
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 19
MH  - Exons
MH  - Female
MH  - Hemiplegia/*genetics/pathology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Polymorphism, Single-Stranded Conformational
MH  - Reference Values
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
AID - 10.1212/wnl.53.1.34 [doi]
PST - ppublish
SO  - Neurology. 1999 Jul 13;53(1):34-7. doi: 10.1212/wnl.53.1.34.