Are there CAG repeat expansion-related disorders outside the central nervous system?

Paola Ferro, Raffaella Dell'Eva, Ulrich Pfeffer

Research output: Contribution to journalArticle


Expansions of poly-glutamine tracts in proteins that are expressed in the central nervous system cause neurodegenerative diseases. The altered proteins accumulate over long periods of time, forming nuclear inclusions, and lead to neuronal cell death. A similar mechanism could also be operant in non-dividing cells outside the central nervous system because nuclear inclusions are not limited to neurons. In addition, variations of the repeat length within the normal range may affect cellular function as it has been shown for the androgen receptor that is involved in neoplastic degeneration of several tissues. We have identified a poly-glutamine/poly-proline repeat in the homeobox gene DLX6. DLX genes are expressed in non-proliferative cells of the apical ectodermal ridge of developing limbs. Ablation of these cells leads to limb malformation. We propose that CAG triplet expansions in this gene could lead to cell death in the apical ectodermal ridge causing limb malformations. Indeed, autosomal dominant limb malformations with increasing severity in successive generations have been linked to the chromosomal region that contains DLX6. The analysis of a limited number of patients affected by split hand/foot malformation so far revealed only a slight modifier effect of repeat length within the normal range and no expansions have been detected.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalBrain Research Bulletin
Issue number3-4
Publication statusPublished - Nov 1 2001


  • Anticipation
  • Apical ectodermal ridge
  • DLX
  • Homeobox gene
  • Limb morphogenesis
  • Neurodegeneration
  • Poly-glutamine
  • Striatum
  • Triplet repeat expansion

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Are there CAG repeat expansion-related disorders outside the central nervous system?'. Together they form a unique fingerprint.

  • Cite this