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Mohr-Tranebjaerg syndrome (MTS) (formerly DFN-1) is an X-linked neurodegenerative syndrome characterized by prelingual or postlingual sensorineural hearing loss, progressive dystonia and visual impairment. In addition, psychiatric symptoms, cognitive impairment and behavioural problems may appear. Early-onset deafness is the only pathognomonic symptom; all other clinical signs vary in their degree of severity and clinical course. A multifocal and progressive neurodegeneration, affecting distinct areas of the CNS is typically found in patients suffering from MTS. MTS is a very rare disorder of unknown prevalence. The underlying genetic defects are found in the TIMM8A/DDP1 gene located on chromosome Xq22. Most of the mutations described so far are inactivating mutations such as stop mutations, insertions and deletions. Only two missense mutations have been reported: one affects the ATG start codon (M1I), the other results in the substitution of a highly conserved cysteine residue (C66W). Both mutations result in complete loss of the TIMM8A/DDP1 gene product. DDP1/TIMM8A encodes a small polypeptide of 97 amino acid residues, the deafness-dystonia peptide 1 (DDP1). Functional studies revealed that DDP1 is localized to the mitochondria, and plays a role in the import of nuclear-encoded preproteins into the mitochondrial inner membrane. Loss of DDP1 leads to impairment of specific mitochondrial functions and, subsequently, to degeneration of neuronal cells. As with other mitochondrial disorders, there is no specific treatment for MTS. |