RGD Reference Report - Otopathology in Mohr-Tranebjaerg syndrome. - Rat Genome Database

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Otopathology in Mohr-Tranebjaerg syndrome.

Authors: Bahmad, Fayez  Merchant, Saumil N  Nadol, Joseph B  Tranebjaerg, Lisbth 
Citation: Bahmad F, etal., Laryngoscope. 2007 Jul;117(7):1202-8.
RGD ID: 13209136
Pubmed: PMID:17471106   (View Abstract at PubMed)
PMCID: PMC2515094   (View Article at PubMed Central)
DOI: DOI:10.1097/MLG.0b013e3180581944   (Journal Full-text)

BACKGROUND: Mohr-Tranebjaerg syndrome (MTS) is an X-linked, recessive, syndromic sensorineural hearing loss (HL) characterized by onset of deafness in childhood followed later in adult life by progressive neural degeneration affecting the brain and optic nerves. MTS is caused by mutations in the DDP/TIMM8A gene, which encodes for a 97 amino acid polypeptide; this polypeptide is a translocase of the inner mitochondrial membrane.
OBJECTIVES: To describe the otologic presentation and temporal bone histopathology in four affected individuals with MTS.
MATERIAL AND METHODS: All four subjects belonged to a large, multigenerational Norwegian family and were known to carry a frame shift mutation in the TIMM8A gene. Temporal bones were removed at autopsy and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria vascularis, and cochlear neuronal cells. Vestibular neurons were also counted.
RESULTS: All four subjects developed progressive HL in early childhood, becoming profoundly deaf by the age of 10 years. All four developed language, and at least one subject used amplification in early life. Audiometric evaluation in two subjects showed 80- to 100-dB HL by the age of 10 years. The subjects died between the ages of 49 and 67. The otopathology was strikingly similar in that all bones examined showed near-total loss of cochlear neuronal cells and severe loss of vestibular neurons. When compared with age-matched controls, there was 90% to 95% loss of cochlear neurons and 75% to 85% loss of vestibular neurons.
CONCLUSIONS: We infer that the HL in MTS is likely to be the result of a postnatal and progressive degeneration of cochlear neurons and that MTS constitutes a true auditory neuropathy. Our findings have implications for clinical diagnosis of patients with MTS and management of the HL.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TIMM8AHumandeafness-dystonia-optic neuronopathy syndrome  IAGP DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 
Timm8a1Ratdeafness-dystonia-optic neuronopathy syndrome  ISOTIMM8A (Homo sapiens)DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 
Timm8a1Mousedeafness-dystonia-optic neuronopathy syndrome  ISOTIMM8A (Homo sapiens)DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TIMM8AHumanAbnormality of the cochlear nerve  IAGP associated with Mohr-Tranebjaerg Syndrome and DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 
TIMM8AHumanAbnormality of the vestibular nerve  IAGP associated with Mohr-Tranebjaerg Syndrome and DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 
TIMM8AHumanHearing impairment  IAGP associated with Mohr-Tranebjaerg Syndrome and DNA:mutation:exon:116delT(Q38fsX64)(human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Timm8a1  (translocase of inner mitochondrial membrane 8A1)

Genes (Mus musculus)
Timm8a1  (translocase of inner mitochondrial membrane 8A1)

Genes (Homo sapiens)
TIMM8A  (translocase of inner mitochondrial membrane 8A)

Additional Information