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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
Novel splice site CACNA1A mutation causing episodic ataxia type 2.
M A Kaunisto1, H Harno, M Kallela
1Biomedicum Helsinki, Molecular Medicine Research Program, University of Helsinki, Helsinki, Finland.
Neurogenetics
|October 8, 2003
Summary
Episodic ataxia type 2 (EA-2), a neurological disorder, is linked to CACNA1A gene mutations. A novel splice site mutation was identified in a family, expanding the known mutation spectrum for EA-2.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Episodic ataxia type 2 (EA-2) is an autosomal dominant neurological disorder.
- Symptoms include ataxia, vertigo, nausea, nystagmus, and fatigue, often responsive to acetazolamide.
- EA-2 is associated with mutations in the CACNA1A gene encoding the P/Q-type calcium channel alpha-1A subunit.
Purpose of the Study:
- To investigate the genetic cause of EA-2 in a large family.
- To identify novel mutations in the CACNA1A gene associated with EA-2.
Main Methods:
- Family-based linkage analysis to the chromosome 19p13.2 locus.
- DNA sequencing of the CACNA1A gene to identify mutations.
Main Results:
- A two-point maximum LOD score of 4.48 was achieved, confirming linkage to the CACNA1A locus.
- A novel CACNA1A mutation, IVS36-2A>G, was identified at the 3' acceptor splice site of intron 36.
- This represents the first described CACNA1A acceptor splice site mutation and the most C-terminal EA-2 mutation found to date.
Conclusions:
- The identified IVS36-2A>G mutation in CACNA1A is the likely cause of EA-2 in this family.
- This finding expands the spectrum of known EA-2-causing mutations and highlights the importance of splice site mutations.
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