rss
J Med Genet 43:441-443 doi:10.1136/jmg.2005.039230
  • Short report

Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia

  1. A Bouhouche,
  2. A Benomar,
  3. N Bouslam,
  4. T Chkili,
  5. M Yahyaoui
  1. Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, Rabat, Morocco
  1. Correspondence to:
 Dr A Bouhouche
 Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, BP 6402, Al Irfane Rabat, Morocco; abouhouche{at}hotmail.com
  • Accepted 21 December 2005
  • Revised 19 December 2005
  • Published Online First 6 January 2006

Abstract

Background: Mutilating sensory neuropathy with spastic paraplegia is a very rare disease with both autosomal dominant and recessive modes of inheritance. We previously mapped the locus of the autosomal recessive form to a 25 cM interval between markers D5S2048 and D5S648 on chromosome 5p. In this candidate interval, the Cct5 gene encoding the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (CCT) was the most obvious candidate gene since mutation in the Cct4 gene encoding the CCT delta subunit has been reported to be associated with autosomal recessive mutilating sensory neuropathy in mutilated foot (mf) rat mutant.

Methods: A consanguineous Moroccan family with four patients displaying mutilating sensory neuropathy associated with spastic paraplegia was investigated. To identify the disease causing gene, the 11 coding exons of the Cct5 gene were screened for mutations by direct sequencing in all family members including the four patients, parents, and six at risk relatives.

Results: Sequence analysis of the Cct5 gene revealed a missense A492G mutation in exon 4 that results in the substitution of a highly conserved histidine for arginine amino acid 147. Interestingly, R147 was absent in 384 control matched chromosomes tested.

Conclusion: This is the first disease causing mutation that has been identified in the human CCT subunit genes; the mf rat mutant could serve as an animal model for studying these chaperonopathies.

Footnotes

  • Published Online First 19 January 2006

  • All authors of this paper are members of the PCNG network “Pôle de Compétences en Neurogénétique” of the Faculté de Médecine et de Pharmacie, of University Mohamed V Souissi (Rabat, Morocco)

  • This research was supported by the Presidency of the University Mohamed V Souissi (Rabat, Morocco) and the Association Marocaine de Neurogénétique (Morocco)

  • Competing interests: none declared