Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes.

Cossee M., Duerr A., Schmitt M., Dahl N., Trouillas P., Allinson P., Kostrzewa M., Nivelon-Chevallier A., Gustavson K.-H., Kohlschuetter A., Mueller U., Mandel J.-L., Brice A., Koenig M., Cavalcanti F., Tammaro A., de Michele G., Filla A., Cocozza S., Labuda M., Montermini L., Poirier J., Pandolfo M.

Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in the first intron of the frataxin gene. The remaining cases are compound heterozygotes for a GAA expansion and a frataxin point mutation. We report here the identification of 10 novel frataxin point mutations, and the detection of a previously described mutation (G130V) in two additional families. Most truncating mutations were in exon 1. All missense mutations were in the last three exons coding for the mature frataxin protein. The clinical features of 25 patients with identified frataxin point mutations were compared with those of 196 patients homozygous for the GAA expansion. A similar phenotype resulted from truncating mutations and from missense mutations in the carboxy-terminal half of mature frataxin, suggesting that they cause a comparable loss of function. In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function. The incidence of optic disk pallor was higher in compound heterozygotes than in expansion homozygotes, which might correlate with a very low residual level of normal frataxin produced from the expanded allele.

Ann. Neurol. 45:200-206(1999) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again