Novel Mutation in AIFM1 Gene Associated with X-Linked Deafness in a Moroccan Family

2021 ◽  
pp. 1-5
Author(s):  
Soukaina Elrharchi ◽  
Zied Riahi ◽  
Sara Salime ◽  
Hicham Charoute ◽  
Lamiae Elkhattabi ◽  
...  
Keyword(s):  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Novel Mutation ◽  
Pedigree Analysis ◽  
Auditory Neuropathy ◽  
Inner Hair Cell ◽  
Whole Exome ◽  
Apoptosis Inducing Factor ◽  
The Impact

<b><i>Introduction:</i></b> Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have either congenital or acquired causes. <b><i>Methods:</i></b> We found a disease-segregating mutation in the X-linked <i>AIFM1</i> gene through whole-exome sequencing, encoding the apoptosis-inducing factor mitochondrion-associated 1. <b><i>Results:</i></b> The impact of the c.1045A&#x3e;G; p.(Ser349Gly) mutation on the AIFM1 protein was predicted using different bioinformatics tools. The pedigree analysis in the examined family was consistent with X-linked dominant inheritance. <b><i>Discussion/Conclusion:</i></b> To our knowledge, this is the first study that identifies a mutation in the <i>AIFM1</i> gene in Moroccan patients suffering from X-linked auditory neuropathy.

scholarly journals Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss

2021 ◽  
Author(s):  
Neil J Ingham ◽  
Navid Banafshe ◽  
Clarisse Panganiban ◽  
Julia L Crunden ◽  
Jing Chen ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Low Frequency ◽  
Auditory Brainstem ◽  
Auditory Neuropathy ◽  
Mutant Mice ◽  
Inner Hair Cell ◽  
Apical Half

ABSTRACTAge-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency hearing impairment in two mutant mouse lines, carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Auditory brainstem response (ABR) thresholds (a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies. Klhl18 mutant mice exhibit an uncommon low frequency hearing impairment with physiological features consistent with Auditory Neuropathy Spectrum Disorder (ANSD).SIGNIFICANCE STATEMENTWe describe a novel progressive hearing loss in Klhl18 mutant mice that affects the lower frequencies of its’ hearing range. Investigation of two mutant alleles of this gene revealed primary inner hair cell defects affecting the neural output of the cochlea while outer hair cell function appeared normal. The tallest stereocilia of inner hair cells showed an abnormal tapering shape, especially notable in the apical half of the cochlear duct corresponding to the low frequency hearing loss. Our finding of a primary inner hair cell defect associated with raised thresholds for auditory brainstem responses combined with normal outer hair cell function suggests that Klhl18 deficiency and inner hair cell pathology may contribute to Auditory Neuropathy Spectrum Disorder in humans.

scholarly journals A Case Report on Familial origin of Auditory Neuropathy Spectrum Disorder

2020 ◽  
pp. 1-9
Author(s):  
Sabarish A ◽  
◽  
Harshavardhan Raje Urs P ◽  
Keyword(s):  
Case Report ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Auditory Neuropathy ◽  
Spectrum Disorder ◽  
Hearing Disorder ◽  
Inner Hair Cell ◽  
Genetic Trait ◽  
Auditory Neuropathy Spectrum Disorder ◽  
Related Risk

Auditory neuropathy Spectrum Disorder (ANSD) is a unique hearing disorder where outer hair cell status is found to be normal, but inner hair cell and/or the synaptic connections to the auditory nerve is disrupted. It is a diverse group of hearing disorder which can be manifested either congenitally or can be late in onset. However, there are various etiologies of auditory neuropathy which is represented in the literature, which includes birth related risk factors for hearing loss like prematurity, bilirubin synthesis issues, lack of oxygen supply to the baby during or after delivery, and genetic actors. It is estimated that approximately 40% of cases have an underlying causal factor as genetic origin, which can be inherited in either syndromic or non-syndromic way. The below case report provides an extra support for the fundamental genetic trait in ANSD. The study presents two congenital ANSD cases where, both children were diagnosed as congenital ANSD

Masking Effects in Patients With Auditory Neuropathy—Possible Involvement of Suppression Mechanism Caused by Normal Outer Hair Cell Function

2013 ◽  
Vol 34 (5) ◽  
pp. 868-876
Author(s):  
Kazuha Oda ◽  
Tetsuaki Kawase ◽  
Yusuke Takata ◽  
Hiromitsu Miyazaki ◽  
Hiroshi Hidaka ◽  
...  
Keyword(s):  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Auditory Neuropathy ◽  
Suppression Mechanism

scholarly journals Evaluation of outer hair cell function and medial olivocochlear efferent system in patients with type II diabetes mellitus

2014 ◽  
Vol 44 ◽  
pp. 150-156 ◽  
Author(s):  
Hayriye KARABULUT ◽  
İsmail KARABULUT ◽  
Muharrem DAĞLI ◽  
Yıldırım Ahmet BAYAZIT ◽  
Şule BİLEN ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hair Cell ◽  
Type Ii Diabetes ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Efferent System ◽  
Medial Olivocochlear ◽  
Medial Olivocochlear Efferent System

scholarly journals Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function

2017 ◽  
Vol 38 (1) ◽  
pp. e1-e12 ◽  
Author(s):  
Naomi F. Bramhall ◽  
Dawn Konrad-Martin ◽  
Garnett P. McMillan ◽  
Susan E. Griest
Keyword(s):  
Hair Cell ◽  
Auditory Brainstem Response ◽  
Noise Exposure ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Auditory Brainstem ◽  
Brainstem Response

scholarly journals RHOMutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Satoshi Katagiri ◽  
Takaaki Hayashi ◽  
Masakazu Akahori ◽  
Takeshi Itabashi ◽  
Jo Nishino ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Conformational Transition ◽  
Novel Mutation ◽  
The Novel ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Modeling Analysis ◽  
Whole Exome ◽  
The Impact

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).Methods. Whole-exome sequence analysis was performed in ten adRP families. IdentifiedRHOmutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of theRHOmutation on the rhodopsin conformation was examined by molecular modeling analysis.Results. In two adRP families, we identified twoRHOmutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification ofRHOmutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

Electrical Stimulation of the Auditory Nerve via Cochlear Implants in Patients with Auditory Neuropathy

2002 ◽  
Vol 111 (5_suppl) ◽  
pp. 29-31 ◽  
Author(s):  
Yvonne S. Sininger ◽  
Patricia Trautwein
Keyword(s):  
Electrical Stimulation ◽  
Cochlear Implants ◽  
Auditory Nerve ◽  
Otoacoustic Emissions ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Auditory Neuropathy ◽  
Auditory Brain Stem Response ◽  
Average Performance ◽  
Auditory Brain Stem

Auditory neuropathy (AN) is a term used to describe an auditory disorder in which there is evidence of normal outer hair cell function (otoacoustic emissions and/or cochlear microphonics) and poor function of the auditory nerve (absent or highly distorted auditory brain stem response starting with wave I). Many of these patients have evidence of generalized peripheral nerve disease, leading to an assumption that the peripheral portion of the auditory nerve is the most likely site of lesion. A small group of these patients has received cochlear implants, and the majority of them achieve average to above-average performance. Although this outcome may seem incongruous with neural disease, average performance by patients with AN may be a result of the reintroduction of neural synchrony by electrical stimulation and/or the fact that most deaf patients have poor nerve survival. Although cochlear implants are promising for deaf patients with AN, more study of the disorder is needed.

scholarly journals Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258158
Author(s):  
Neil J. Ingham ◽  
Navid Banafshe ◽  
Clarisse Panganiban ◽  
Julia L. Crunden ◽  
Jing Chen ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Cell Function ◽  
Low Frequency ◽  
Mutant Mice ◽  
Auditory Brainstem Responses ◽  
Distortion Product Otoacoustic Emission ◽  
Inner Hair Cell ◽  
Distortion Product ◽  
Age Related

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.

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