Medizinische Universität Graz - Research portal
Selected Publication:
Lee, MJ; Stephenson, DA; Groves, MJ; Sweeney, MG; Davis, MB; An, SF; Houlden, H; Salih, MA; Timmerman, V; de Jonghe, P; Auer-Grumbach, M; Di Maria, E; Scaravilli, F; Wood, NW; Reilly, MM.
Hereditary sensory neuropathy is caused by a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4 ) gene.
Hum Mol Genet. 2003; 12(15):1917-1925
Doi: 10.1093/hmg/ddg198
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-authors Med Uni Graz
- Auer-Grumbach Michaela
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- A spontaneous autosomal recessive mutation was identified in the Sprague-Dawley rat strain with an early onset sensory neuropathy. The main clinical features of the mutation (mutilated foot, mf ), detectable shortly after birth, include ataxia, insensitivity to pain and foot ulceration. The pathological features include a severe reduction in the number of sensory ganglia and fibres. This mutant is therefore an excellent model for human hereditary sensory neuropathies. Here, we demonstrate that the mf locus maps to the distal end of rat chromosome 14, a region syntenic to human 2p13-p16 and proximal mouse 11. Sequence analysis of four candidate genes in this interval revealed a 1349G>A mutation in the chaperonin (delta) subunit 4 (Cct4) gene associated with the mf mutant. This change resulted in the substitution of a highly conserved cysteine for tyrosine at amino acid 450. Although we did not identify a mutation in the human CCT4 gene in a set of HSN patients, this result clearly demonstrates the pathological consequences of a defect in Cct4, a subunit of CCT (cytosolic chaperonin-containing t-complex peptide-1), involved in folding tubulin, actin and other cytosolic proteins. This is the first report of a mutation in a molecular chaperonin causing a hereditary neuropathy and raises the possibility that mis-folding proteins may be a cause of this group of neuropathies.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Blotting, Northern -
- Chaperonins - genetics
- Chromosome Mapping - genetics
- Chromosomes, Human, Pair 2 - genetics
- DNA Primers - genetics
- Disease Models, Animal - genetics
- Gene Expression - genetics
- Genes, Recessive - genetics
- Hereditary Sensory and Autonomic Neuropathies - genetics
- Humans - genetics
- Lod Score - genetics
- Molecular Sequence Data - genetics
- Mutation, Missense - genetics
- Rats - genetics
- Rats, Mutant Strains - genetics
- Rats, Sprague-Dawley - genetics
- Reverse Transcriptase Polymerase Chain Reaction - genetics
- Sequence Analysis, DNA - genetics