A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome

Arch Neurol. 2005 Feb;62(2):306-8. doi: 10.1001/archneur.62.2.306.

Abstract

Background: X-linked dystonia-deafness syndrome (Mohr-Tranebjaerg syndrome) is a rare neurodegenerative disease characterized by hearing loss and dystonia. So far, 7 mutations in the coding region of the DDP1 gene have been described. They consist of frameshift, nonsense, missense mutations or deletions.

Objective: To investigate the presence of mutations in the DDP1 gene in a family with dystonia-deafness syndrome.

Design: Seven members belonging to 2 generations of a family with 2 affected subjects underwent genetic analysis. Mutational screening in the DDP1 gene was made through DNA direct sequencing.

Results: We found an intronic mutation in the DDP1 gene. It consists of an A-to-C substitution in the position -23 in reference to the first nucleotide of exon 2 (IVS1-23A>C). The mutation was present in 2 affected men and their respective unaffected mothers, whereas it was absent in the healthy men from this family and in 90 healthy controls.

Conclusions: Intronic mutations in the DDP1 gene can also cause X-linked dystonia-deafness syndrome. In our case, the effect of the mutation could be due to a splicing alteration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Mutational Analysis / methods
  • Deafness / genetics*
  • Family Health
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Introns / genetics*
  • Male
  • Membrane Transport Proteins / genetics*
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mutation / genetics*
  • Pedigree
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • RNA, Messenger
  • TIMM8A protein, human