The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene
Journal Publication ResearchOnline@JCUAbstract
Most cases of Friedreich ataxia (FRDA) are due to expansions of a GAA trinucleotide repeat sequence in the FRDA gene coding for frataxin, a protein of poorly understood function which may regulate mitochondrial iron transport. However, between 1% and 5% of mutations are single base changes in the sequence of the FRDA gene, causing missense, nonsense, or splicing mutations. We describe three new mutations, IVS4nt2 (T to G), R165C, and L182F, which occur in patients in association with GAA expansions. These cases, and a further five reported cases of point mutations causing FRDA, demonstrate that splicing, nonsense, or initiation codon mutations (which cause a complete absence of functional frataxin) are associated with a severe phenotype. Missense mutations, even in highly evolutionally conserved amino acids, may cause a mild or severe phenotype.
Journal
Neurogenetics
Publication Name
Neurogenetics
Volume
1
ISBN/ISSN
1364-6753
Edition
N/A
Issue
4
Pages Count
5
Location
N/A
Publisher
Springer
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Publisher Location
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Publish Date
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Date
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EISSN
N/A
DOI
10.1007/s100480050037