NeuroMolecular Medicine

, Volume 9, Issue 4, pp 285–291

Molecular Genetics of a Patient with Mohr–Tranebjaerg Syndrome due to a New Mutation in the DDP1 Gene

  • José Rafael Blesa
  • Abelardo Solano
  • Paz Briones
  • Jesús Angel Prieto-Ruiz
  • José Hernández-Yago
  • Francisco Coria
Original Paper

DOI: 10.1007/s12017-007-8000-3

Cite this article as:
Blesa, J.R., Solano, A., Briones, P. et al. Neuromol Med (2007) 9: 285. doi:10.1007/s12017-007-8000-3

Abstract

The deafness-dystonia syndrome (DDS) or Mohr–Tranebjaerg syndrome (MTS, MIM 304700) is a rare X-linked recessive neurological disorder resulting from loss-of-function mutations in the nuclear DDP1/TIMM8A gene, involved in the transport and sorting of proteins to the mitochondrial inner membrane. A Mohr–Tranebjaerg patient and his mother were subjected to clinical and molecular studies. Screening of mutations were performed in TIMM8A, TIMM13, and other mitochondrial protein transport genes by conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing of tissue samples from the patient. Mitochondrial DNA of the patient was also sequenced at the genes for COX subunits and some mitochondrial tRNAs. Respiratory chain activities in a muscle biopsy and cultured fibroblasts from the patient were assessed using biochemical methods. mRNA expression of TIMM8A and TIMM13 was determined by RT-PCR in cultured fibroblasts. We identified a new case of Mohr–Tranebjaerg syndrome and report the characteristics of a new pathogenic de novo mutation (c.112C>T, pGln38X) in the TIMM8A gene. Biochemical measures of respiratory chain complex activities in muscle biopsy and fibroblasts did not show a major deficiency or alteration. mRNA expression studies demonstrated increased TIMM8A mRNA levels in cultured fibroblasts from the patient. Phenotypic differences among published cases seem not to be related with the mutation location or type. Our results support the idea that dysfunctions of mitochondrial protein transport, in addition to OXPHOS deficiency, can be the basis of important mitochondrial pathologies.

Keywords

Mohr–Tranebjaerg syndrome DDP1 TIMM8A Deafness-Dystonia Neurodegeneration Recessive X-linked neurodegenerative disorder Deafness-Dystonia-Optic neuronopathy syndrome DDON 

Supplementary material

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • José Rafael Blesa
    • 1
  • Abelardo Solano
    • 1
  • Paz Briones
    • 2
  • Jesús Angel Prieto-Ruiz
    • 1
  • José Hernández-Yago
    • 1
  • Francisco Coria
    • 3
  1. 1.Centro de Investigación Príncipe FelipeValenciaSpain
  2. 2.Institut Bioquímica Clínica, Clinic Corporació Sanitaria and CSICBarcelonaSpain
  3. 3.Clinic for Neurological DisordersPalma de MallorcaSpain