Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature
<i>Background and objectives</i>: Otoferlin is a multi-C2 domain protein implicated in neurotransmitter-containing vesicle release and replenishment of the cochlear inner hair cell (IHC) synapses. Mutations in the OTOF gene have been associated with two different clinical phenotypes: a p...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/2/352 |
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| author | Francesca Forli Silvia Capobianco Stefano Berrettini Luca Bruschini Silvia Romano Antonella Fogli Veronica Bertini Francesco Lazzerini |
| author_facet | Francesca Forli Silvia Capobianco Stefano Berrettini Luca Bruschini Silvia Romano Antonella Fogli Veronica Bertini Francesco Lazzerini |
| author_sort | Francesca Forli |
| collection | DOAJ |
| description | <i>Background and objectives</i>: Otoferlin is a multi-C2 domain protein implicated in neurotransmitter-containing vesicle release and replenishment of the cochlear inner hair cell (IHC) synapses. Mutations in the OTOF gene have been associated with two different clinical phenotypes: a prelingual severe-to-profound sensorineural hearing loss (ANSD-DFNB9); and the peculiar temperature-sensitive auditory neuropathy (TS-ANSD), characterized by a baseline mild-to-moderate hearing threshold that worsens to severe-to-profound when the body temperature rises that returns to a baseline a few hours after the temperature has fallen again. The latter clinical phenotype has been described only with a few OTOF variants with an autosomal recessive biallelic pattern of inheritance. Case report: A 7-year-old boy presented a picture compatible with TS-ANSD exacerbated by febrile states or physical exercise with mild-to-moderate hearing loss at low and medium frequencies and a decrease in speech discrimination that worsened with an unfavorable speech-to-noise ratio. Otoacoustic emissions (OAEs) were present whereas auditory brainstem responses (ABRs) evoked by a click or tone-burst were generally absent. No inner ear malformations were described from the CT scan or MRI. Next-generation sequencing (NGS) of the known deafness genes and multi-phasic bioinformatic analyses of the data detected in OTOF a c.2521G>A missense variant and the deletion of 7.4 Kb, which was confirmed by array-comparative genomic hybridization (array-CGH). The proband’s parents, who were asymptomatic, were tested by Sanger sequencing and the father presented the c.2521G>A missense variant. <i>Conclusions</i>: The picture presented by the patient was compatible with OTOF-induced TS-ANSD. OTOF has been generally associated with an autosomal recessive biallelic pattern of inheritance; in this clinical report, two pathogenic variants never previously associated with TS-ANSD were described. |
| first_indexed | 2024-03-11T08:26:55Z |
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| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T08:26:55Z |
| publishDate | 2023-02-01 |
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| series | Medicina |
| spelling | doaj.art-108e00f1849344719210f179399e76c52023-11-16T22:00:36ZengMDPI AGMedicina1010-660X1648-91442023-02-0159235210.3390/medicina59020352Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current LiteratureFrancesca Forli0Silvia Capobianco1Stefano Berrettini2Luca Bruschini3Silvia Romano4Antonella Fogli5Veronica Bertini6Francesco Lazzerini7ENT, Audiology and Phoniatrics Unit, University of Pisa, 56124 Pisa, ItalyENT, Audiology and Phoniatrics Unit, University of Pisa, 56124 Pisa, ItalyENT, Audiology and Phoniatrics Unit, University of Pisa, 56124 Pisa, ItalyENT, Audiology and Phoniatrics Unit, University of Pisa, 56124 Pisa, ItalyDepartment of Medical and Oncological Area, Section of Medical Genetics, Azienda Ospedaliero Universitaria Pisana, 56124 Pisa, ItalyDepartment of Laboratory Medicine, Section of Molecular Genetics, Azienda Ospedaliero Universitaria Pisana, 56124 Pisa, ItalyDepartment of Laboratory Medicine, Section of Cytogenetics, Azienda Ospedaliero Universitaria Pisana, 56124 Pisa, ItalyENT, Audiology and Phoniatrics Unit, University of Pisa, 56124 Pisa, Italy<i>Background and objectives</i>: Otoferlin is a multi-C2 domain protein implicated in neurotransmitter-containing vesicle release and replenishment of the cochlear inner hair cell (IHC) synapses. Mutations in the OTOF gene have been associated with two different clinical phenotypes: a prelingual severe-to-profound sensorineural hearing loss (ANSD-DFNB9); and the peculiar temperature-sensitive auditory neuropathy (TS-ANSD), characterized by a baseline mild-to-moderate hearing threshold that worsens to severe-to-profound when the body temperature rises that returns to a baseline a few hours after the temperature has fallen again. The latter clinical phenotype has been described only with a few OTOF variants with an autosomal recessive biallelic pattern of inheritance. Case report: A 7-year-old boy presented a picture compatible with TS-ANSD exacerbated by febrile states or physical exercise with mild-to-moderate hearing loss at low and medium frequencies and a decrease in speech discrimination that worsened with an unfavorable speech-to-noise ratio. Otoacoustic emissions (OAEs) were present whereas auditory brainstem responses (ABRs) evoked by a click or tone-burst were generally absent. No inner ear malformations were described from the CT scan or MRI. Next-generation sequencing (NGS) of the known deafness genes and multi-phasic bioinformatic analyses of the data detected in OTOF a c.2521G>A missense variant and the deletion of 7.4 Kb, which was confirmed by array-comparative genomic hybridization (array-CGH). The proband’s parents, who were asymptomatic, were tested by Sanger sequencing and the father presented the c.2521G>A missense variant. <i>Conclusions</i>: The picture presented by the patient was compatible with OTOF-induced TS-ANSD. OTOF has been generally associated with an autosomal recessive biallelic pattern of inheritance; in this clinical report, two pathogenic variants never previously associated with TS-ANSD were described.https://www.mdpi.com/1648-9144/59/2/352temperature-sensitive auditory neuropathyOTOFotoferlindeafnesstargeted next-generation sequencing |
| spellingShingle | Francesca Forli Silvia Capobianco Stefano Berrettini Luca Bruschini Silvia Romano Antonella Fogli Veronica Bertini Francesco Lazzerini Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature Medicina temperature-sensitive auditory neuropathy OTOF otoferlin deafness targeted next-generation sequencing |
| title | Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature |
| title_full | Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature |
| title_fullStr | Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature |
| title_full_unstemmed | Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature |
| title_short | Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature |
| title_sort | temperature sensitive auditory neuropathy report of a novel variant of otof gene and review of current literature |
| topic | temperature-sensitive auditory neuropathy OTOF otoferlin deafness targeted next-generation sequencing |
| url | https://www.mdpi.com/1648-9144/59/2/352 |
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