Friedreich's ataxia with chorea and myoclonus caused by a compound heterozygosity for a novel deletion and the trinucleotide GAA expansion.
Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting about 1 in 50,000 individuals. It is caused by mutations in the frataxin gene; 98% of cases have homozygous expansions of a GAA trinucleotide in intron 1 of the frataxin gene. The remaining 2% of patients are compound heterozygotes, who have a GAA repeat expansion in one allele and a point mutation in the other allele. FRDA patients with point mutation have been suggested to have atypical clinical features. We present a case of compound heterozygotes in a FRDA patient who has a deletion of one T in the start codon (ATG) of the frataxin gene and a GAA repeat expansion in the other allele. The patient presented with chorea and subsequently developed FRDA symptoms. The disease in this case is the result of both a failure of initiation of translation and the effect of the expansion. This novel mutation extends the range of point mutations seen in FRDA patients, and also broadens the spectrum of FRDA genotype associated with chorea.
Neurobiology Department, ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, NSW, Australia. danqing@med.usyd.edu.au
Danqing
D
Zhu
Christopher
C
Burke
Anthony
A
Leslie
Garth A
GA
Nicholson
D000293:Adolescent; D002819:Chorea / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005621:Friedreich Ataxia / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D033862:Iron-Binding Proteins; D008297:Male; D009207:Myoclonus / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D017354:Point Mutation; D017384:Sequence Deletion; D019680:Trinucleotide Repeat Expansion; D000096923:Frataxin
D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin