Abstract
We discovered intronic mutations in two episodic ataxia type 2 (EA2) families: a four-nucleotide GAGT deletion at IVS41+(3-6) and a single nucleotide insertion (insT) at IVS24+3. We expressed minigenes harboring the mutations in cell lines to demonstrate exon skipping from the deletion mutation and the activation of a cryptic splice donor site from the insertion mutation. The identification of these disease-causing mutations expands the spectrum of EA2 mutations and emphasizes the importance of intronic sequences in regulating gene expression.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Adult
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Animals
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Ataxia / genetics*
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COS Cells
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Calcium Channels, L-Type
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Child
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Chlorocebus aethiops
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DNA Mutational Analysis / methods
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Exons
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Family Health
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Female
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Genetic Predisposition to Disease
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Humans
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Introns*
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Male
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Mutation*
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Nerve Tissue Proteins / genetics*
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RNA Splicing / physiology
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RNA, Small Nuclear / physiology
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Transfection / methods
Substances
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CACNA1C protein, human
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Calcium Channels, L-Type
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Nerve Tissue Proteins
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RNA, Small Nuclear