X2S gene micromutations in Friedreich's ataxia alleles not carrying the GAA expansion

C. Gellera, S. Botti, B. Castellotti, M. C. Riggio, G. Uziel, D. Pareyson, S. Didonato, F. Taroni

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Friedreich's ataxia (FA) is the most common autosomal recessive ataxia with an extimated prevalence of 1:50,000 The FA gene (X25) has been recently identified and characterized. Approx. 94% of FA patients are homozygous for an unstable GAA tnnucleotide expansion within intron 1 (normal subjects: 7-22 repeat units) In our series of 124 patients (113 families), the expanded alleles ranged 170-1200 GAA units. We report here the molecular study of 7 additional families, in which patients were heterozygous for both an expanded and a nonexpanded allele. To search for the presence of X25 micromutations on the nonexpanded allele, X25 exons were analyzed by SSCP and automated sequencing. One patient was found to be heterozygous for a previously reported missense mutation, an Ilel54Phe substitution (Filla et al., 1996), which thus appears to be relatively frequent among Italian FA patients A second patient carried a novel micronyitation at the cxon 3-intron 3 boundary, a 13-bp deletion which eliminates the last 4 bp of exon 3 and the splice donor site of intron 3. Molecular analysis in the remaining patients are currently under way. The presence of X25 micromutations in FA alleles not harboring the GAA expansion strongly supports the pathogenic role of the X25 gene in FA Functional analysis of these mutant X25 products will help in elucidating the molecular pathogenesis of Friedreich's ataxia.

Original languageEnglish
Pages (from-to)25
Number of pages1
JournalItalian Journal of Neurological Sciences
Issue number4
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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