title: Frataxin point mutations in two patients with Friedreich's ataxia and unusual clinical features.
abstract: Two patients with a progressive ataxia are presented with clinical features consistent with classic Friedreich's ataxia (FRDA), but also with features unusual for FRDA. Analysis of DNA showed that each patient is heterozygous for the expanded GAA repeat of FRDA, but carries a base change on his other frataxin allele. For one patient a non-conservative arginine to cysteine amino acid change is predicted at amino acid 165 whereas the other mutation is found at the junction of exon one and intron one. Muscle biopsy showed an absence of frataxin immunoreactivity in the patient harbouring the intronic mutation, confirming the pathological nature of the base change. These mutations extend the range of point mutations seen in FRDA, and agree with recent reports suggesting phenotypic variation in patients with FRDA harbouring point mutations in conjunction with an expanded GAA repeat.
authors.affiliation: Departments of Neurology, Pediatrics, and Pharmacology, Division of Neuroscience Research, Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: McCormack
authors.forename: R P
authors.initials: RP
authors.lastname: Guttmann
authors.forename: M
authors.initials: M
authors.lastname: Schumann
authors.forename: J M
authors.initials: JM
authors.lastname: Farmer
authors.forename: C A
authors.initials: CA
authors.lastname: Stolle
authors.forename: V
authors.initials: V
authors.lastname: Campuzano
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: D R
authors.initials: DR
authors.lastname: Lynch
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D005621:Friedreich Ataxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D033862:Iron-Binding Proteins; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D018911:Trinucleotide Repeats; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin