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Auditory impairment in H‐ABC tubulinopathy
Author(s) -
LopezJuarez Alejandra,
GonzalezVega Arturo,
KleinertAltamirano Anke,
Piazza Valeria,
GardunoRobles Angeles,
Alata Milvia,
VillaseñorMora Carlos,
Eguibar Jose R.,
Cortes Carmen,
Padierna Luis Carlos,
Hernandez Victor H.
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.24990
Subject(s) - ataxia , atrophy , cerebellum , biology , auditory brainstem response , white matter , audiology , auditory neuropathy , neuroscience , pathology , brainstem , basal ganglia , presbycusis , hearing loss , central nervous system , magnetic resonance imaging , medicine , radiology
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.