Neurogenetics

, Volume 1, Issue 4, pp 253–257

The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene

  • S. M. Forrest
  • Melanie Knight
  • Martin B. Delatycki
  • Damien Paris
  • Robert Williamson
  • John King
  • Leone Yeung
  • Najah Nassif
  • Garth A. Nicholson
Original article

ABSTRACT

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.

Key words Point mutation Friedreich ataxia GAA expansion Phenotype 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • S. M. Forrest
    • 1
  • Melanie Knight
    • 1
  • Martin B. Delatycki
    • 1
  • Damien Paris
    • 1
  • Robert Williamson
    • 1
  • John King
    • 2
  • Leone Yeung
    • 3
  • Najah Nassif
    • 3
  • Garth A. Nicholson
    • 3
  1. 1.Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Flemington Road, Parkville, Victoria, 3052, AustraliaAU
  2. 2.Department of Neurology, Royal Melbourne Hospital, Parkville, 3052, AustraliaAU
  3. 3.University of Sydney Department of Medicine, Molecular Medicine Laboratory, Concord Hospital, 2137, NSW, AustraliaAU

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