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Acta Neuropathologica

, Volume 97, Issue 2, pp 139–142 | Cite as

Markedly different course of Friedreich’s ataxia in sib pairs with similar GAA repeat expansions in the frataxin gene

  • T. Klopstock
  • S. Chahrokh-Zadeh
  • E. Holinski-Feder
  • A. Meindl
  • T. Gasser
  • D. Pongratz
  • W. Müller-Felber
Regular paper

Abstract

Friedreich’s ataxia (FA) is most frequently caused by intronic trinucleotide repeat expansions in the frataxin gene on chromosome 9. The broad clinical spectrum includes late-onset FA (LOFA) and FA with retained reflexes (FARR). The size of the GAA expansions accounts for most, but not all, of the clinical variability. We report the unusual occurrence of LOFA and FARR in two siblings of patients with classical early-onset FA in two families. In spite of the markedly different course of the disease, the respective siblings harboured GAA repeat expansions of similar size in leucocytes. Since haplotype-related variability is not likely among siblings, we suppose that this intrafamilial phenotype variability is due to somatic mosaicism, with the more severely affected siblings harbouring the larger expansions in spinal cord and other affected tissues. In view of these results, genetic counseling and predictions on the course of FA are particularly difficult, even if an expansion mutation is found.

Key words Friedreich’s ataxia Trinucleotide repeat expansion Frataxin gene Intrafamilial variability Genetic counseling 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • T. Klopstock
    • 1
  • S. Chahrokh-Zadeh
    • 2
  • E. Holinski-Feder
    • 2
  • A. Meindl
    • 2
  • T. Gasser
    • 1
  • D. Pongratz
    • 3
  • W. Müller-Felber
    • 3
  1. 1.Department of Neurology, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, D-81 366 Munich, Germany e-mail: klopstock@brain.nefo.med.uni-muenchen.de, Tel.: +49-89-7095-2687, Fax: +49-89-7095-3677DE
  2. 2.Department of Medical Genetics, University of Munich, D-80 336 Munich, GermanyDE
  3. 3.Friedrich-Baur-Institut, University of Munich, D-80 336 Munich, GermanyDE

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