Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever!

Marlin, Sandrine; Feldmann, Delphine; Nguyen, Yann; Rouillon, Isabelle; Loundon, Natalie; Jonard, Laurence; Bonnet, Crystel; Couderc, Rémy; Garabédian, E. N.; Petit, Christine; Denoyelle, Françoise

doi:10.1016/j.bbrc.2010.03.062

Cited by 75 publications

(84 citation statements)

References 22 publications

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“…It has the audiological signature of auditory neuropathy, and was suspected to reflect a defect of pre synaptic function in inner hair cells 42 soon after its char acterization. During the past decade, rare cases of less severe otoferlinrelated auditory synapt opathies have been reported [43][44][45][46][47] . In some patients with these disorders, an elevation in body temperature (even by only 1 o C) as a result of exercise or fever [43][44][45][46][47] can exacerbate the condi tion into complete deafness accompanied by tinnitus.…”

Section: Genetic Auditory Synaptopathiesmentioning

confidence: 99%

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Auditory neuropathy — neural and synaptic mechanisms

2016

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Section: Genetic Auditory Synaptopathiesmentioning

confidence: 99%

“…To date, six OTOF mutations have been associated with temperature sensitive deafness [43][44][45][46][47] . The 'pachanga' missense otoferlin mouse mutant, generated in a forward genetic screen 61 , provided important additional insight into the function of otoferlin.…”

Section: Genetic Auditory Synaptopathiesmentioning

confidence: 99%

Auditory neuropathy — neural and synaptic mechanisms

2016

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“…Some mutations of this group deviate from the usual phenotype, however, suggesting a conditional or residual function of the mutated proteins. Among them, six mutations (p.I515T, p.G541S, p.G614E, p.R1080P, p.R1607W, and p.E1804del) have been reported in patients with a temperaturesensitive phenotype (Marlin et al, 2010;Matsunaga et al, 2012;Romanos et al, 2009;Varga et al, 2006;Wang et al, 2010). In addition, mutation p.E1700Q (which affects a residue in the linker region between domains C2E and C2F) results in progressive hearing loss that may range in severity from mild to profound (Chiu et al, 2010).…”

Section: Spectrum Of Otof Mutationsmentioning

confidence: 99%

“…Some individuals harboring missense mutations in the OTOF gene suffer from a particular disorder called temperature-sensitive auditory neuropathy (Marlin et al, 2010;Starr et al, 1998;Varga et al, 2006;Wynne et al, 2013). When afebrile, these patients have normal or only mildly elevated hearing thresholds.…”

Section: Clinical Features Of Otof-related Auditory Neuropathymentioning

confidence: 99%

Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations

et al. 2015

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Mutations in the OTOF gene encoding otoferlin result in a disrupted function of the ribbon synapses with an impaired multivesicular glutamate release. Most affected subjects present with congenital hearing loss and abnormal auditory brainstem potentials associated with preserved cochlear hair cell activities (otoacoustic emissions, cochlear microphonics [CMs]). Transtympanic electrocochleography (ECochG) has recently been proposed for defining the details of potentials arising in both the cochlea and auditory nerve in this disorder, and with a view to shedding light on the pathophysiological mechanisms underlying auditory dysfunction.\ud We review the audiological and electrophysiological findings in children with congenital profound deafness carrying two mutant alleles of the OTOF gene. We show that cochlear microphonic (CM) amplitude, summating potential (SP) amplitude and latency are normal, consistently with a preserved outer and inner hair cell function. In the majority of OTOF children, the SP component is followed by a markedly prolonged low-amplitude negative potential by comparison with the compound action potential (CAP) recorded in normally-hearing children. This potential is identified at intensities as low as 90 dB below the behavioral threshold. In some ears, a synchronized CAP is superimposed on the prolonged responses at high intensity. Stimulation at high rates reduces the amplitude and duration of the prolonged potentials, consistently with their neural generation. In some children, however, the ECochG response only consists of the SP, with no prolonged potential. Cochlear implants restore hearing sensitivity, speech perception and neural CAP by electrically stimulating the auditory nerve fibers.\ud These findings indicate that an impaired multivesicular glutamate release in OTOF-related disorders leads to abnormal auditory nerve fiber activation and a consequent impairment of spike generation. The magnitude of these effects seems to vary, ranging from no auditory nerve fiber activation to an abnormal generation of EPSPs that occasionally trigger a synchronized electrical activity, resulting in high-threshold CAPs

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“…The magnitude of their speech comprehension deficits is larger than expected from the patients' degree of audibility changes, and reflects impaired processing of auditory temporal cues (Starr et al, 1996;Zeng et al, 2005). Specific etiologies for the disorder affect both pre-synaptic sites (e.g., impaired function of ribbon synapses of inner hair cells; Varga et al, 2006;Marlin et al, 2010) and post-synaptic sites (e.g., impaired function of auditory nerve fibers; Starr et al, 2003). Detailed analyses of the word processing errors in a group of AN subjects with Freidreich's ataxia, a post-synaptic disorder of neural transmission, showed abnormal identification of stop consonants distinguished by VOT (/tu//du/, /ba/ /pa/, /ka/ /ga/) but normal classification of sibilant consonants containing high frequencies (e.g., /s/ vs. /f/).…”

Section: Introductionmentioning

confidence: 99%