title: Clinical and genetic study of Friedreich ataxia in an Australian population.
abstract: Friedreich ataxia is an autosomal recessive disorder caused by mutations in the FRDA gene that encodes a 210-amino acid protein called frataxin. An expansion of a GAA trinucleotide repeat in intron 1 of the gene is present in more than 95% of mutant alleles. Of the 83 people we studied who have mutations in FRDA, 78 are homozygous for an expanded GAA repeat; the other five patients have an expansion in one allele and a point mutation in the other. Here we present a detailed clinical and genetic study of a subset of 51 patients homozygous for an expansion of the GAA repeat. We found a correlation between the size of the smaller of the two expanded alleles and age at onset, age into wheelchair, scoliosis, impaired vibration sense, and the presence of foot deformity. There was no significant correlation between the size of the smaller allele and cardiomyopathy, diabetes mellitus, loss of proprioception, or bladder symptoms. The larger allele size correlated with bladder symptoms and the presence of foot deformity. The duration of disease is correlated with wheelchair use and the presence of diabetes, scoliosis, bladder symptoms and impaired proprioception, and vibration sense but no other complications studied.
authors.affiliation: The Murdoch Institute, Royal Children's Hospital, Victoria, Australia. delatycm@cryptic.rch.unimelb.edu.au
authors.forename: M B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: D B
authors.initials: DB
authors.lastname: Paris
authors.forename: R J
authors.initials: RJ
authors.lastname: Gardner
authors.forename: G A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: N
authors.initials: N
authors.lastname: Nassif
authors.forename: E
authors.initials: E
authors.lastname: Storey
authors.forename: J C
authors.initials: JC
authors.lastname: MacMillan
authors.forename: V
authors.initials: V
authors.lastname: Collins
authors.forename: R
authors.initials: R
authors.lastname: Williamson
authors.forename: S M
authors.initials: SM
authors.lastname: Forrest
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001315:Australia; D009202:Cardiomyopathies / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D033862:Iron-Binding Proteins; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011434:Proprioception / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics* / Q000502:physiology; D001745:Urinary Bladder Diseases / Q000235:genetics; D014910:Wheelchairs; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin