Auditory impairment in H-ABC tubulinopathy
| Autor: | Arturo González-Vega, Luis Carlos Padierna, Victor H. Hernandez, Carmen María Aránzazu Cejudo Cortés, Jose R. Eguibar, Alejandra Lopez-Juarez, Valeria Piazza, Carlos Villaseñor-Mora, Angeles Garduno‐Robles, Anke Kleinert‐Altamirano, Milvia Alata |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cochlear Nucleus Male medicine.medical_specialty Cerebellum Ataxia Developmental Disabilities Hearing Loss Sensorineural Mutation Missense Audiology Biology Rats Mutant Strains Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Atrophy Tubulin Basal ganglia otorhinolaryngologic diseases medicine Animals Humans Point Mutation Spasticity Myelin Sheath medicine.diagnostic_test General Neuroscience Magnetic resonance imaging medicine.disease Inferior Colliculi Rats Disease Models Animal 030104 developmental biology Auditory brainstem response medicine.anatomical_structure Amino Acid Substitution Organ of Corti Dystonic Disorders Child Preschool Ear Inner Auditory Perception Evoked Potentials Auditory Female medicine.symptom 030217 neurology & neurosurgery Demyelinating Diseases |
| Zdroj: | The Journal of comparative neurologyREFERENCES. 529(5) |
| ISSN: | 1096-9861 |
| Popis: | Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H-ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H-ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II-IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H-ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies. |
| Databáze: | OpenAIRE |
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