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Sample records for hearing gene prestin

  1. The hearing gene Prestin reunites echolocating bats

    PubMed Central

    Li, Gang; Wang, Jinhong; Rossiter, Stephen J.; Jones, Gareth; Cotton, James A.; Zhang, Shuyi

    2008-01-01

    The remarkable high-frequency sensitivity and selectivity of the mammalian auditory system has been attributed to the evolution of mechanical amplification, in which sound waves are amplified by outer hair cells in the cochlea. This process is driven by the recently discovered protein prestin, encoded by the gene Prestin. Echolocating bats use ultrasound for orientation and hunting and possess the highest frequency hearing of all mammals. To test for the involvement of Prestin in the evolution of bat echolocation, we sequenced the coding region in echolocating and nonecholocating species. The resulting putative gene tree showed strong support for a monophyletic assemblage of echolocating species, conflicting with the species phylogeny in which echolocators are paraphyletic. We reject the possibilities that this conflict arises from either gene duplication and loss or relaxed selection in nonecholocating fruit bats. Instead, we hypothesize that the putative gene tree reflects convergence at stretches of functional importance. Convergence is supported by the recovery of the species tree from alignments of hydrophobic transmembrane domains, and the putative gene tree from the intra- and extracellular domains. We also found evidence that Prestin has undergone Darwinian selection associated with the evolution of specialized constant-frequency echolocation, which is characterized by sharp auditory tuning. Our study of a hearing gene in bats strongly implicates Prestin in the evolution of echolocation, and suggests independent evolution of high-frequency hearing in bats. These results highlight the potential problems of extracting phylogenetic signals from functional genes that may be prone to convergence. PMID:18776049

  2. Prestin and high frequency hearing in mammals

    PubMed Central

    Zhang, Shuyi; Liu, Yang

    2011-01-01

    Recent evidence indicates that the evolution of ultrasonic hearing in echolocating bats and cetaceans has involved adaptive amino acid replacements in the cochlear gene prestin. A substantial number of these changes have occurred in parallel in both groups, suggesting that particular amino acid residues might confer greater auditory sensitivity to high frequencies. Here we review some of these findings, and consider whether similar signatures of prestin protein sequence evolution also occur in mammals that possess high frequency hearing for passive localization and conversely, whether this gene has undergone less change in mammals that lack high frequency hearing. PMID:21655450

  3. Parallel sites implicate functional convergence of the hearing gene prestin among echolocating mammals.

    PubMed

    Liu, Zhen; Qi, Fei-Yan; Zhou, Xin; Ren, Hai-Qing; Shi, Peng

    2014-09-01

    Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/α, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/α and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Prestin Regulation and Function in Residual Outer Hair Cells after Noise-Induced Hearing Loss

    PubMed Central

    Xia, Anping; Song, Yohan; Wang, Rosalie; Gao, Simon S.; Clifton, Will; Raphael, Patrick; Chao, Sung-il; Pereira, Fred A.; Groves, Andrew K.; Oghalai, John S.

    2013-01-01

    The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. TectaC1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9–12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30–40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9–12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32–58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to

  5. Prestin regulation and function in residual outer hair cells after noise-induced hearing loss.

    PubMed

    Xia, Anping; Song, Yohan; Wang, Rosalie; Gao, Simon S; Clifton, Will; Raphael, Patrick; Chao, Sung-il; Pereira, Fred A; Groves, Andrew K; Oghalai, John S

    2013-01-01

    The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta(C1509G) transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9-12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30-40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9-12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32-58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to

  6. Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.

    PubMed

    Cheatham, Mary Ann; Edge, Roxanne M; Homma, Kazuaki; Leserman, Emily L; Dallos, Peter; Zheng, Jing

    2015-01-01

    A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification.

  7. Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice

    PubMed Central

    Cheatham, Mary Ann; Edge, Roxanne M.; Homma, Kazuaki; Leserman, Emily L.; Dallos, Peter; Zheng, Jing

    2015-01-01

    A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI’s were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin’s motor function in cochlear amplification. PMID:26682723

  8. Prestin is an anion transporter dispensable for mechanical feedback amplification in Drosophila hearing.

    PubMed

    Kavlie, Ryan G; Fritz, Janice L; Nies, Florian; Göpfert, Martin C; Oliver, Dominik; Albert, Joerg T; Eberl, Daniel F

    2015-01-01

    In mammals, the membrane-based protein Prestin confers unique electromotile properties to cochlear outer hair cells, which contribute to the cochlear amplifier. Like mammals, the ears of insects, such as those of Drosophila melanogaster, mechanically amplify sound stimuli and have also been reported to express Prestin homologs. To determine whether the D. melanogaster Prestin homolog (dpres) is required for auditory amplification, we generated and analyzed dpres mutant flies. We found that dpres is robustly expressed in the fly's antennal ear. However, dpres mutant flies show normal auditory nerve responses, and intact non-linear amplification. Thus we conclude that, in D. melanogaster, auditory amplification is independent of Prestin. This finding resonates with prior phylogenetic analyses, which suggest that the derived motor function of mammalian Prestin replaced, or amended, an ancestral transport function. Indeed, we show that dpres encodes a functional anion transporter. Interestingly, the acquired new motor function in the phylogenetic lineage leading to birds and mammals coincides with loss of the mechanotransducer channel NompC (=TRPN1), which has been shown to be required for auditory amplification in flies. The advent of Prestin (or loss of NompC, respectively) may thus mark an evolutionary transition from a transducer-based to a Prestin-based mechanism of auditory amplification.

  9. Membrane Prestin Expression Correlates with the Magnitude of Prestin-Associated Charge Movement

    PubMed Central

    Seymour, Michelle L.; Rajagopalan, Lavanya; Duret, Guillaume; Volk, Matthew J.; Liu, Haiying; Brownell, William E.; Pereira, Fred A.

    2016-01-01

    Full expression of electromotility, generation of non-linear capacitance (NLC), and high-acuity mammalian hearing require prestin function in the lateral wall of cochlear outer hair cells (OHCs). Estimates of the number of prestin molecules in the OHC membrane vary, and a consensus has not emerged about the correlation between prestin expression and prestin-associated charge movement in the OHC. Using an inducible prestin-expressing cell line, we demonstrate that the charge density, but not the voltage at peak capacitance, directly correlates with the amount of prestin in the plasma membrane. This correlation is evident in studies involving a controlled increase of prestin expression with time after induction and inducer dose-response. Conversely, membrane prestin levels and charge density gradually decline together following the reduction of prestin levels from a steady state by removal of the inducer. Thus, charge density directly correlates with the level of membrane prestin expression, whereas changing membrane levels of prestin have no effect on the voltage at peak capacitance in this inducible prestin-expressing cell line. PMID:27262187

  10. Reduction in Noise-Induced Functional Loss of the Cochleae in Mice with Pre-Existing Cochlear Dysfunction Due to Genetic Interference of Prestin

    PubMed Central

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation. PMID:25486270

  11. Reduction in noise-induced functional loss of the cochleae in mice with pre-existing cochlear dysfunction due to genetic interference of prestin.

    PubMed

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation.

  12. Prestin modulates mechanics and electromechanical force of the plasma membrane.

    PubMed

    Zhang, Rui; Qian, Feng; Rajagopalan, Lavanya; Pereira, Fred A; Brownell, William E; Anvari, Bahman

    2007-07-01

    The voltage-dependent movement, or electromotility, of cochlear outer hair cells contributes to cochlear amplification in mammalian hearing. Outer hair-cell electromotility involves a membrane-based motor in which the membrane protein prestin plays a central role. We have investigated the contribution of prestin to the mechanics and electromechanical force (EMF) generation of the membrane using membrane tethers formed from human embryonic kidney (HEK) cells. Several measures of membrane tether mechanics are greater in tethers pulled from HEK cells transfected with prestin when compared to control untransfected HEK cells. A single point mutation of alanine to tryptophan (A100W) in prestin eliminates prestin-associated charge movement and diminishes EMF but does not alter passive membrane mechanics. These results suggest that prestin-associated charge transfer is necessary for maximal EMF generation by the membrane.

  13. Prestin and the good vibrations

    PubMed Central

    Birke, Anna Sofia; Javelle, Arnaud

    2016-01-01

    In a recent paper published in the Biochemical Journal, Lolli et al. presented evidence that the C-terminal STAS (sulfate transporter and anti-sigma factor antagonist) domain of the motor protein prestin possesses an anion-binding site. This discovery might shed light on an aspect of the function of this mysterious and fascinating protein that is crucial for the human hearing system. PMID:27470595

  14. Analysis of the oligomeric structure of the motor protein prestin.

    PubMed

    Zheng, Jing; Du, Guo-Guang; Anderson, Charles T; Keller, Jacob P; Orem, Alex; Dallos, Peter; Cheatham, MaryAnn

    2006-07-21

    Prestin, a member of the solute carrier family 26, is expressed in the basolateral membrane of outer hair cells. This protein provides the molecular basis for outer hair cell somatic electromotility, which is crucial for the frequency selectivity and sensitivity of mammalian hearing. It has long been known that there are abundantly expressed approximately 11-nM protein particles present in the basolateral membrane. These particles were hypothesized to be the motor proteins that drive electromotility. Because the calculated size of a prestin monomer is too small to form an approximately 11-nM particle, the possibility of prestin oligomerization was examined. We investigated possible quaternary structures of prestin by lithium dodecyl sulfate-PAGE, perfluoro-octanoate-PAGE, a membrane-based yeast two-hybrid system, and chemical cross-linking experiments. Prestin, obtained from different host or native cells, is resistant to dissociation by lithium dodecyl sulfate and behaves as a stable oligomer on lithium dodecyl sulfate-PAGE. In the membrane-based yeast two-hybrid system, homo-oligomeric interactions between prestin-bait/prestin-prey suggest that prestin molecules can associate with each other. Chemical cross-linking experiments, perfluoro-octanoate-PAGE/Western blot, and affinity purification experiments all indicate that prestin exists as a higher order oligomer, such as a tetramer, in prestin-expressing yeast, mammalian cell lines and native outer hair cells. Our data from experiments using hydrophobic and hydrophilic reducing reagents suggest that the prestin dimer is connected by a disulfide bond embedded in the prestin hydrophobic core. This stable dimer may act as the building block for producing the higher order oligomers that form the approximately 11-nM particles in the outer hair cell's basolateral membrane.

  15. Interaction between the motor protein prestin and the transporter protein VAPA.

    PubMed

    Sengupta, Soma; Miller, Katharine K; Homma, Kazuaki; Edge, Roxanne; Cheatham, Mary Ann; Dallos, Peter; Zheng, Jing

    2010-07-01

    Prestin is the motor protein responsible for cochlear outer hair cell (OHC) somatic electromotility. Eliminating this abundant basolateral membrane protein not only causes loss of frequency selectivity and hearing sensitivity, but also leads to OHC death. A membrane-based yeast two-hybrid approach was used to screen an OHC-enriched cDNA (complementary Deoxyribonucleic Acid) library in order to identify prestin-associated proteins. Several proteins were recognized as potential prestin partners, including vesicle-associated membrane protein associated protein A (VAPA or VAP-33). VAPA is an integral membrane protein that plays an important role in membrane trafficking, endoplasmic reticulum homeostasis, and the stress-signaling system. The connection between VAPA and prestin was confirmed through co-immunoprecipitation experiments. This new finding prompted the investigation of the interaction between VAPA and prestin in outer hair cells. By comparing VAPA expression between wild-type OHCs and OHCs derived from prestin-knockout mice, we found that VAPA is expressed in OHCs and the quantity of VAPA expressed is related to the presence of prestin. In other words, less VAPA protein is found in OHCs lacking prestin. Thus, prestin appears to modify the expression of VAPA protein in OHCs. Intriguingly, more prestin protein appears at the plasma membrane when VAPA is co-expressed with prestin. These data suggest that VAPA could be involved in prestin's transportation inside OHCs and may facilitate the targeting of this abundant OHC protein to the plasma membrane.

  16. Stable Expression of the Motor Protein Prestin in Chinese Hamster Ovary Cells

    NASA Astrophysics Data System (ADS)

    Iida, Koji; Konno, Kazuaki; Oshima, Takeshi; Tsumoto, Kouhei; Ikeda, Katsuhisa; Kumagai, Izumi; Kobayashi, Toshimitsu; Wada, Hiroshi

    Mammalian hearing sensitivity relies on a mechanical amplification mechanism involving the outer hair cells (OHCs), which rapidly alter their longitudinal length in response to changes in their membrane potential. The molecular basis of this mechanism is thought to be a motor protein embedded in the lateral membrane of the OHCs. Recently, this motor protein was identified and termed prestin. Since then, prestin has been researched intensively to elucidate the behavior of the OHCs. However, little progress in the study of prestin at the molecular level has been made because no method of obtaining an adequate amount of prestin has been established. In this study, therefore, an attempt was made to construct a stable expression system of prestin using Chinese hamster ovary (CHO) cells. The expression of prestin in the transfected CHO cells and the activity of prestin on CHO cells were confirmed by immunofluorescence and whole-cell patch-clamp measurements, respectively.

  17. Interaction between CFTR and prestin (SLC26A5).

    PubMed

    Homma, Kazuaki; Miller, Katharine K; Anderson, Charles T; Sengupta, Soma; Du, Guo-Guang; Aguiñaga, Salvador; Cheatham, Maryann; Dallos, Peter; Zheng, Jing

    2010-06-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that is present in a variety of epithelial cell types, and usually expressed in the luminal membrane. In contrast, prestin (SLC26A5) is a voltage-dependent motor protein, which is present in the basolateral membrane of cochlear outer hair cells (OHCs), and plays an important role in the frequency selectivity and sensitivity of mammalian hearing. By using in situ hybridization and immunofluorescence, we found that both mRNA and protein of CFTR are present in OHCs, and that CFTR localizes in both the apical and the lateral membranes. CFTR was not detected in the lateral membrane of inner hair cells (IHCs) or in that of OHCs derived from prestin-knockout mice, i.e., in instances where prestin is not expressed. These results suggest that prestin may interact physically with CFTR in the lateral membrane of OHCs. Immunoprecipitation experiments confirmed a prestin-CFTR interaction. Because chloride is important for prestin function and for the efferent-mediated inhibition of cochlear output, the prestin-directed localization of CFTR to the lateral membrane of OHCs has a potential physiological significance. Aside from its role as a chloride channel, CFTR is known as a regulator of multiple protein functions, including those of the solute carrier family 26 (SLC26). Because prestin is in the SLC26 family, several members of which interact with CFTR, we explored the potential modulatory relationship associated with a direct, physical interaction between prestin and CFTR. Electrophysiological experiments demonstrated that cAMP-activated CFTR is capable of enhancing voltage-dependent charge displacement, a signature of OHC motility, whereas prestin does not affect the chloride conductance of CFTR.

  18. High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.

    PubMed

    Tang, Hsiao-Yuan; Xia, Anping; Oghalai, John S; Pereira, Fred A; Alford, Raye L

    2005-08-08

    Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which

  19. Glycosylation regulates prestin cellular activity.

    PubMed

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  20. Localization of prestin and expression in the early period after radiation in mice.

    PubMed

    Yang, Chen; Zhang, Wei; Liu, Xiao-Long; Liang, Yong; Yuan, Ya-Wei; Ren, Chen; Peng, Jin-Hao

    2014-12-01

    This study aimed to examine expression and microstructural distribution of prestin in outer hair cells, and the effect of dose and time of radiation on prestin expression in the BALB/c mouse. We also investigated the molecular biological characteristics of prestin and possible mechanisms of sensorineural hearing loss caused by radiation. Seventy 4-week-old mice were randomly divided into four groups, including one control group and three experimental groups. Each experimental group was randomly divided into two groups, which were killed to collect specimens of the cochlea on the 3rd and 7th days after exposure to different doses of 8, 12, and 16 Gy radiation. These cochleas were embedded in paraffin, and then cut into sections. The sections were immunostained with anti-prestin antibodies. The distribution of prestin was observed under optical microscopy and the density of prestin-positive expression was quantitatively calculated by Image-Pro Plus. Prestin had high expression in the lateral membrane and low expression in the cytoplasm of outer hair cells above the nucleus. The density of prestin protein expression of the basal turn was not significantly different after exposure to the different doses of radiation compared with the control group, but up-regulation occurred after radiation in the apex turn. We conclude that prestin protein is mainly expressed in the lateral membrane above the nucleus. Prestin protein may be responsible for the mechanism of injury to the inner ear caused by radiation.

  1. Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

    2016-05-01

    Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.

  2. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats

    PubMed Central

    2016-01-01

    Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs) of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6) for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs. PMID:28097024

  3. Relationship between Fluorescence Intensity of GFP and the Expression Level of Prestin in a Prestin-Expressing Chinese Hamster Ovary Cell Line

    NASA Astrophysics Data System (ADS)

    Iida, Koji; Nagaoka, Tomoyuki; Tsumoto, Kouhei; Ikeda, Katsuhisa; Kumagai, Izumi; Kobayashi, Toshimitsu; Wada, Hiroshi

    Outer hair cells (OHCs) in mammals can elongate and contract at frequencies up to 100kHz in response to changes in their membrane potential. The origin of this unique motility is the motor protein prestin, which is densely packed in the lateral membrane of the OHCs. In a previous work, we constructed a prestin-expressing cell line using Chinese hamster ovary (CHO) cells to obtain a stable supply of prestin. When we research prestin using constructed cells, it is necessary to estimate the expression level of prestin in the cells easily and non-invasively. As the prestin gene and a green fluorescent protein (GFP) gene were introduced into constructed cells using the same vector, the expression level of prestin and fluorescence intensity of GFP are possibly correlated. Since this correlation is not clear, however, in this study, we therefore investigated whether the expression level of prestin evaluated by patch-clamp recording and the fluorescence intensity of GFP obtained from fluorescence images are correlated or not. As a result, it was demonstrated that they were correlated. The expression level of prestin can therefore be evaluated by measuring the fluorescence intensity of GFP.

  4. Genes and Hearing Loss

    MedlinePlus

    ... a rare allele of a gene by a single heterozygous parent is sufficient to generate an affected child. A heterozygous parent has two types of the ... help them determine their risk of having a child with hearing problems. Patient Health Home Copyright © 2017 ... Development Practice Management ENT Careers Marketplace Privacy Policy Terms ...

  5. Hear, hear: the convergent evolution of echolocation in bats?

    PubMed

    Teeling, Emma C

    2009-07-01

    The evolutionary history of laryngeal echolocation is controversial, and little is known about the molecular mechanisms that underlie this sense. A recent paper by Li and colleagues is one of the first studies to identify and sequence a gene involved in echolocation in bats -Prestin, the so-called mammalian hearing gene. Phylogenetic analyses show evidence for positive selection acting on this gene in the echolocating lineages and support the convergent evolution of laryngeal echolocation in bats.

  6. DNA Sequence Analysis of SLC26A5, Encoding Prestin, in a Patient-Control Cohort: Identification of Fourteen Novel DNA Sequence Variations

    PubMed Central

    Minor, Jacob S.; Tang, Hsiao-Yuan; Pereira, Fred A.; Alford, Raye Lynn

    2009-01-01

    Background Prestin, encoded by the gene SLC26A5, is a transmembrane protein of the cochlear outer hair cell (OHC). Prestin is required for the somatic electromotile activity of OHCs, which is absent in OHCs and causes severe hearing impairment in mice lacking prestin. In humans, the role of sequence variations in SLC26A5 in hearing loss is less clear. Although prestin is expected to be required for functional human OHCs, the clinical significance of reported putative mutant alleles in humans is uncertain. Methodology/Principal Findings To explore the hypothesis that SLC26A5 may act as a modifier gene, affecting the severity of hearing loss caused by an independent etiology, a patient-control cohort was screened for DNA sequence variations in SLC26A5 using sequencing and allele specific methods. Patients in this study carried known pathogenic or controversial sequence variations in GJB2, encoding Connexin 26, or confirmed or suspected sequence variations in SLC26A5; controls included four ethnic populations. Twenty-three different DNA sequence variations in SLC26A5, 14 of which are novel, were observed: 4 novel sequence variations were found exclusively among patients; 7 novel sequence variations were found exclusively among controls; and, 12 sequence variations, 3 of which are novel, were found in both patients and controls. Twenty-one of the 23 DNA sequence variations were located in non-coding regions of SLC26A5. Two coding sequence variations, both novel, were observed only in patients and predict a silent change, p.S434S, and an amino acid substitution, p.I663V. In silico analysis of the p.I663V amino acid variation suggested this variant might be benign. Using Fisher's exact test, no statistically significant difference was observed between patients and controls in the frequency of the identified DNA sequence variations. Haplotype analysis using HaploView 4.0 software revealed the same predominant haplotype in patients and controls and derived haplotype blocks

  7. Genes and Syndromic Hearing Loss.

    ERIC Educational Resources Information Center

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  8. Genes and Syndromic Hearing Loss.

    ERIC Educational Resources Information Center

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  9. A highly expressing Tet-inducible cell line recapitulates in situ developmental changes in prestin's Boltzmann characteristics and reveals early maturational events.

    PubMed

    Bian, Shumin; Koo, Bon W; Kelleher, Stephen; Santos-Sacchi, Joseph; Navaratnam, Dhasakumar S

    2010-10-01

    Prestin is the motor protein within the lateral membrane of outer hair cells (OHCs), and it is required for mammalian cochlear amplification. Expression of prestin precedes the onset of hearing in mice, and it has been suggested that prestin undergoes a functional maturation within the membrane coincident with the onset of hearing. We have developed a tetracycline-inducible prestin-expressing cell line that we have used to model prestin's functional maturation. We used prestin's voltage-dependent nonlinear charge movement (or nonlinear capacitance) as a test of function and correlated it to biochemical measures of prestin expressed on the cell surface. An initial stage of slow growth in charge density is accompanied by a rapid increase in our estimate of charge carried by an individual motor. A rapid growth in charge density follows and strongly correlates with an increasing ratio between an apparently larger and smaller monomer, suggesting that the latter exerts a dominant-negative effect on function. Finally, there is a gradual depolarizing shift in the voltage of peak capacitance, similar to that observed in developing OHCs. This inducible system offers many opportunities for detailed studies of prestin.

  10. Parallel signatures of sequence evolution among hearing genes in echolocating mammals: an emerging model of genetic convergence.

    PubMed

    Davies, K T J; Cotton, J A; Kirwan, J D; Teeling, E C; Rossiter, S J

    2012-05-01

    Recent findings of sequence convergence in the Prestin gene among some bats and cetaceans suggest that parallel adaptations for high-frequency hearing have taken place during the evolution of echolocation. To determine if this gene is an exception, or instead similar processes have occurred in other hearing genes, we have examined Tmc1 and Pjvk, both of which are associated with non-syndromic hearing loss in mammals. These genes were amplified and sequenced from a number of mammalian species, including echolocating and non-echolocating bats and whales, and were analysed together with published sequences. Sections of both genes showed phylogenetic signals that conflicted with accepted species relationships, with coding regions uniting laryngeal echolocating bats in a monophyletic clade. Bayesian estimates of posterior probabilities of convergent and divergent substitutions provided more direct evidence of sequence convergence between the two groups of laryngeal echolocating bats as well as between echolocating bats and dolphins. We found strong evidence of positive selection acting on some echolocating bat species and echolocating cetaceans, contrasting with purifying selection on non-echolocating bats. Signatures of sequence convergence and molecular adaptation in two additional hearing genes suggest that the acquisition of high-frequency hearing has involved multiple loci.

  11. Parallel signatures of sequence evolution among hearing genes in echolocating mammals: an emerging model of genetic convergence

    PubMed Central

    Davies, K T J; Cotton, J A; Kirwan, J D; Teeling, E C; Rossiter, S J

    2012-01-01

    Recent findings of sequence convergence in the Prestin gene among some bats and cetaceans suggest that parallel adaptations for high-frequency hearing have taken place during the evolution of echolocation. To determine if this gene is an exception, or instead similar processes have occurred in other hearing genes, we have examined Tmc1 and Pjvk, both of which are associated with non-syndromic hearing loss in mammals. These genes were amplified and sequenced from a number of mammalian species, including echolocating and non-echolocating bats and whales, and were analysed together with published sequences. Sections of both genes showed phylogenetic signals that conflicted with accepted species relationships, with coding regions uniting laryngeal echolocating bats in a monophyletic clade. Bayesian estimates of posterior probabilities of convergent and divergent substitutions provided more direct evidence of sequence convergence between the two groups of laryngeal echolocating bats as well as between echolocating bats and dolphins. We found strong evidence of positive selection acting on some echolocating bat species and echolocating cetaceans, contrasting with purifying selection on non-echolocating bats. Signatures of sequence convergence and molecular adaptation in two additional hearing genes suggest that the acquisition of high-frequency hearing has involved multiple loci. PMID:22167055

  12. The Evolution of Prestin: Examination with Membrane Thickness Sensitivity

    NASA Astrophysics Data System (ADS)

    Izumi, Chisako; Bird, Jonathan; Schächinger, Torsten; Oliver, Dominik; Iwasa, Kuni H.

    2011-11-01

    Prestin (SLC26A5) is a membrane protein that is essential for electromotility of outer hair cells and, in turn, for the cochlear amplifier. This function is mammalian innovation and prestin orthologs in non-mammalian hair cells function as anion exchangers rather than a motile element. Taking advantage of this evolutionary change, we found that the sensitivity of prestin orthologs to membrane thickness is inversely related to their effectiveness for the motile function. In addition, a chimera between zebrafish prestin and rat prestin, which shows motile functionality, has membrane thickness sensitivity lower than any prestin ortholog we have examined, confirming the relationship.

  13. Analysis of Membrane Topology of Prestin Expressing in CHO Cells

    NASA Astrophysics Data System (ADS)

    Murakoshi, Michio; Kawase, Tomohiro; Kumano, Shun; Wada, Hiroshi

    2011-11-01

    Outer hair cell (OHC) motility is thought to be based on the voltage-dependent conformational changes of the motor protein prestin. However, little is known about its structure and function. In this study, the membrane topology of prestin was investigated by single molecule force spectroscopy using an atomic force microscope (AFM). The C-terminus of prestin was tagged with an Avi-tag and biotinylated. Prestin was then connected with a streptavidin-coated AFM cantilever via biotin-streptavidin binding. The prestin was pulled out from the plasma membrane by retracting the cantilever and force curves were obtained. Obtained force curves suggested the existence of 12 transmembrane domains of prestin.

  14. Voltage-sensitive prestin orthologue expressed in zebrafish hair cells

    PubMed Central

    Albert, Jörg T; Winter, Harald; Schaechinger, Thorsten J; Weber, Thomas; Wang, Xiang; He, David Z Z; Hendrich, Oliver; Geisler, Hyun-Soon; Zimmermann, Ulrike; Oelmann, Katrin; Knipper, Marlies; Göpfert, Martin C; Oliver, Dominik

    2007-01-01

    Prestin, a member of the solute carrier (SLC) family SLC26A, is the molecular motor that drives the somatic electromotility of mammalian outer hair cells (OHCs). Its closest reported homologue, zebrafish prestin (zprestin), shares ∼70% strong amino acid sequence similarity with mammalian prestin, predicting an almost identical protein structure. Immunohistochemical analysis now shows that zprestin is expressed in hair cells of the zebrafish ear. Similar to mammalian prestin, heterologously expressed zprestin is found to generate voltage-dependent charge movements, giving rise to a non-linear capacitance (NLC) of the cell membrane. Compared with mammalian prestin, charge movements mediated by zprestin display a weaker voltage dependence and slower kinetics; they occur at more positive membrane voltages, and are not associated with electromotile responses. Given this functional dissociation of NLC and electromotility and the structural similarity with mammalian prestin, we anticipate that zprestin provides a valuable tool for tracing the molecular and evolutionary bases of prestin motor function. PMID:17272340

  15. Ion and solute transport by Prestin in Drosophila and Anopheles.

    PubMed

    Hirata, Taku; Czapar, Anna; Brin, Lauren; Haritonova, Alyona; Bondeson, Daniel P; Linser, Paul; Cabrero, Pablo; Thompson, James; Dow, Julian A T; Romero, Michael F

    2012-04-01

    The gut and Malpighian tubules of insects are the primary sites of active solute and water transport for controlling hemolymph and urine composition, pH, and osmolarity. These processes depend on ATPase (pumps), channels and solute carriers (Slc proteins). Maturation of genomic databases enables us to identify the putative molecular players for these processes. Anion transporters of the Slc4 family, AE1 and NDAE1, have been reported as HCO(3)(-) transporters, but are only part of the story. Here we report Dipteran (Drosophila melanogaster (d) and Anopheles gambiae (Ag)) anion exchangers, belonging to the Slc26 family, which are multi-functional anion exchangers. One Drosophila and two Ag homologues of mammalian Slc26a5 (Prestin) and Slc26a6 (aka, PAT1, CFEX) were identified and designated dPrestin, AgPrestinA and AgPrestinB. dPrestin and AgPrestinB show electrogenic anion exchange (Cl(-)/nHCO(3)(-), Cl(-)/SO(4)(2-) and Cl(-)/oxalate(2-)) in an oocyte expression system. Since these transporters are the only Dipteran Slc26 proteins whose transport is similar to mammalian Slc26a6, we submit that Dipteran Prestin are functional and even molecular orthologues of mammalian Slc26a6. OSR1 kinase increases dPrestin ion transport, implying another set of physiological processes controlled by WNK/SPAK signaling in epithelia. All of these mRNAs are highly expressed in the gut and Malpighian tubules. Dipteran Prestin proteins appear suited for central roles in bicarbonate, sulfate and oxalate metabolism including generating the high pH conditions measured in the Dipteran midgut lumen. Finally, we present and discuss Drosophila genetic models that integrate these processes.

  16. Ion and solute transport by prestin in Drosophila and Anopheles

    PubMed Central

    Hirata, Taku; Czapar, Anna; Brin, Lauren R.; Haritonova, Alyona; Bondeson, Daniel P.; Linser, Paul J.; Cabrero, Pablo; Dow, Julian A. T.; Romero, Michael F.

    2012-01-01

    The gut and Malpighian tubules of insects are the primary sites of active solute and water transport for controlling hemolymph and urine composition, pH, and osmolarity. These processes depend on ATPase (pumps), channels and solute carriers (Slc proteins). Maturation of genomic databases enables us to identify the putative molecular players for these processes. Anion transporters of the Slc4 family, AE1 and NDAE1, have been reported as HCO3− transporters, but are only part of the story. Here we report Dipteran (Drosophila melanogaster (d) and Anopheles gambiae (Ag)) anion exchangers, belonging to the Slc26 family, which are multi-functional anion exchangers. One Drosophila and two Ag homologues of mammalian Slc26a5 (prestin) and Slc26a6 (aka, PAT1, CFEX) were identified and designated dPrestin, AgPrestinA and AgPrestinB. dPrestin and AgPrestinB show electrogenic anion exchange (Cl−/nHCO3−, Cl−/SO42− and Cl−/oxalate2−) in an oocyte expression system. Since these transporters are the only Dipteran Slc26 proteins whose transport is similar to mammalian Slc26a6, we submit that Dipteran Prestin are functional and even molecular orthologues of mammalian Slc26a6. OSR1 kinase increases dPrestin ion transport, implying another set of physiological processes controlled by WNK/SPAK signaling in epithelia. All of these mRNAs are highly expressed in the gut and Malpighian tubules. Dipteran Prestin proteins appear suited for central roles in bicarbonate, sulfate and oxalate metabolism including generating the high pH conditions measured in the Dipteran midgut lumen. Finally, we present and discuss Drosophila genetic models that integrate these processes. PMID:22321763

  17. Functional Regulation of the SLC26-Family Protein Prestin by Calcium/Calmodulin

    PubMed Central

    Keller, Jacob Pearson; Homma, Kazuaki; Duan, Chongwen; Zheng, Jing; Cheatham, Mary Ann

    2014-01-01

    The solute carrier gene family 26 (SLC26) encodes membrane proteins with diverse physiological roles but with the common feature of halide involvement. Here, we present bioinformatic and biochemical evidence that SLC26 proteins have intrinsically disordered regions (IDRs) in their C-terminal domains and that these regions contain calmodulin (CaM) binding sites. The veracity of these predictions and the functional consequences of CaM binding were examined in prestin, SLC26A5, as a model for the SLC26 family and as one of the most investigated and best understood members. We found that CaM binds directly to the IDR in the C-terminal domain of prestin in a calcium-obligate manner. Using both isolated murine outer hair cells (OHCs) and a heterologous expression system, we also found that this calcium-obligate CaM binding shifts the operating point of the protein to more hyperpolarized potentials with consequent alteration of the function of the prestin. Because calcium is the main intracellular second messenger used by the efferent medial olivocochlear (MOC) pathway of the auditory system and CaM is abundant in OHCs, the CaM–prestin interaction may be involved in the MOC-mediated modulation of cochlear amplification. However, this regulatory mechanism is not likely to be restricted to cochlear OHCs, in light of both clear bioinformatic evidence and the fact that calcium and CaM are ubiquitous intracellular second messengers used by virtually all cell types. Hence, the calcium/CaM-dependent regulatory mechanism described herein is likely applicable to most, if not all, SLC26 paralogs. PMID:24453323

  18. A prestin motor in chicken auditory hair cells

    PubMed Central

    Beurg, Maryline; Tan, Xiaodong; Fettiplace, Robert

    2013-01-01

    Active force generation by outer hair cells (OHCs) underlies amplification and frequency tuning in the mammalian cochlea but whether such a process exists in non-mammals is unclear. Here we demonstrate that hair cells of the chicken auditory papilla possess an electromechanical force generator in addition to active hair bundle motion due to mechanotransducer channel gating. The properties of the force generator, its voltage-dependence and susceptibility to salicylate, as well as an associated chloride-sensitive non-linear capacitance, suggest involvement of the chicken homolog of prestin, the OHC motor protein. The presence of chicken prestin in the hair cell lateral membrane was confirmed by immunolabeling studies. The hair bundle and prestin motors together create sufficient force to produce fast lateral displacements of the tectorial membrane. Our results imply that the first use of prestin as a motor protein occurred early in amniote evolution and was not a mammalian invention as is usually supposed. PMID:23746629

  19. Anion transport by the cochlear motor protein prestin.

    PubMed

    Schänzler, Michael; Fahlke, Christoph

    2012-01-15

    Prestin is a member of the SLC26 solute carrier family and functions as a motor protein in cochlear outer hair cells. While other SLC26 homologues were demonstrated to transport a wide variety of anions, no electrogenic transport activity has been assigned so far to mammalian prestin. We here use heterologous expression in mammalian cells, patch clamp recordings and measurements of expression levels of individual cells to study anion transport by rat prestin. We demonstrated that cells expressing rat prestin exhibit SCN(-) currents that are proportional to the number of prestin molecules. Variation of the SCN(-) concentration resulted in changes of the current reversal potential that obey the Nernst equation indicating that SCN(-) transport is not stoichiometrically coupled to other anions. Application of external SCN(-) causes large increases of anion currents, but only minor changes in non-linear charge movements suggesting that only a very small percentage of prestin molecules function as SCN(-) transporters under these conditions. Unitary current amplitudes are below the resolution limit of noise analysis and thus much smaller than expected for pore-mediated anion transport. A comparison with a non-mammalian prestin from D. rerio - recently shown to function as Cl(-)/SO(4)(2-) antiporter - and an SLC26 anion channel, human SLC26A7, revealed that SCN(-) transport is conserved in these distinct members of the SLC26 family. We conclude that mammalian prestin is capable of mediating electrogenic anion transport and suggest that SLC26 proteins converting membrane voltage oscillations into conformational changes and those functioning as channels or transporters share certain transport capabilities.

  20. Membrane thickness sensitivity of prestin orthologs: the evolution of a piezoelectric protein.

    PubMed

    Izumi, Chisako; Bird, Jonathan E; Iwasa, Kuni H

    2011-06-08

    How proteins evolve new functionality is an important question in biology; prestin (SLC26A5) is a case in point. Prestin drives outer hair cell somatic motility and amplifies mechanical vibrations in the mammalian cochlea. The motility of mammalian prestin is analogous to piezoelectricity, in which charge transfer is coupled to changes in membrane area occupied by the protein. Intriguingly, nonmammalian prestin orthologs function as anion exchangers but are apparently nonmotile. We previously found that mammalian prestin is sensitive to membrane thickness, suggesting that prestin's extended conformation has a thinner hydrophobic height in the lipid bilayer. Because prestin-based motility is a mammalian specialization, we initially hypothesized that nonmotile prestin orthologs, while functioning as anion transporters, should be much less sensitive to membrane thickness. We found the exact opposite to be true. Chicken prestin was the most sensitive to thickness changes, displaying the largest shift in voltage dependence. Platypus prestin displayed an intermediate response to membrane thickness and gerbil prestin was the least sensitive. To explain these observations, we present a theory where force production, rather than displacement, was selected for the evolution of prestin as a piezoelectric membrane motor. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.

    PubMed

    Homma, Kazuaki; Duan, Chongwen; Zheng, Jing; Cheatham, Mary Ann; Dallos, Peter

    2013-01-25

    Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer.

  2. Voltage and frequency dependence of prestin-associated charge transfer

    PubMed Central

    Sun, Sean X.; Farrell, Brenda; Chana, Matthew S.; Oster, George; Brownell, William E.; Spector, Alexander A.

    2009-01-01

    Membrane protein prestin is a critical component of the motor complex that generates forces and dimensional changes in cells in response to changes in the cell membrane potential. In its native cochlear outer hair cell, prestin is crucial to the amplification and frequency selectivity of the mammalian ear up to frequencies of tens of kHz. Other cells transfected with prestin acquire voltage-dependent properties similar to those of the native cell. The protein performance is critically dependent on chloride ions, and intrinsic protein charges also play a role. We propose an electro-diffusion model to reveal the frequency and voltage dependence of electric charge transfer by prestin. The movement of the combined charge (i.e., anion and protein charges) across the membrane is described with a Fokker-Planck equation coupled to a kinetic equation that describes the binding of chloride ions to prestin. We found a voltage-and frequency-dependent phase shift between the transferred charge and the applied electric field that determines capacitive and resistive components of the transferred charge. The phase shift monotonically decreases from zero to -90 degree as a function of frequency. The capacitive component as a function of voltage is bell-shaped, and decreases with frequency. The resistive component is bell-shaped for both voltage and frequency. The capacitive and resistive components are similar to experimental measurements of charge transfer at high frequencies. The revealed nature of the transferred charge can help reconcile the high-frequency electrical and mechanical observations associated with prestin, and it is important for further analysis of the structure and function of this protein. PMID:19490917

  3. Prestin is expressed on the whole outer hair cell basolateral surface.

    PubMed

    Yu, Ning; Zhu, Meng-Lei; Zhao, Hong-Bo

    2006-06-20

    Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility. Previous experiments revealed that OHC electromotility and its associated nonlinear capacitance resided in the OHC lateral wall and was not detected at the apical cuticular plate and basal region. In this experiment, the distribution of prestin in adult mouse, rat, and guinea pig OHCs was re-examined by use of immunofluorescent staining and confocal microscopy. We found that prestin labeling was located at the whole OHC basolateral wall, including the basal plasma membrane. However, staining at the basal membrane was weak. As compared with the intensity at the lateral wall, the intensities of prestin labeling at the membrane at the nuclear level and basal pole were 80.5% and 61.1%, respectively. Prestin labeling was not found at the cuticular plate and stereocilia. The prestin labeling was also absent in the cytoplasm and nuclei. The OHC lateral wall above the nuclear level is composed of the plasma membrane, cortical lattice, and subsurface cisternae. By co-staining with di-8-ANEPPS, prestin labeling was found at the outer layer of the OHC lateral wall, which was further evidenced by use of a hypotonic challenge to separate the plasma membrane from the underlying subsurface cisternae. The data revealed that prestin is expressed at the whole OHC basolateral membrane. Prestin in the basal plasma membrane may provide a reservoir on the OHC surface for prestin-recycling and may also facilitate performing its hypothesized transporter function.

  4. The motor protein prestin is a bullet-shaped molecule with inner cavities.

    PubMed

    Mio, Kazuhiro; Kubo, Yoshihiro; Ogura, Toshihiko; Yamamoto, Tomomi; Arisaka, Fumio; Sato, Chikara

    2008-01-11

    Prestin is a transmembrane motor protein localized at the outer hair cells (OHCs) of the mammalian inner ear. Voltage-dependent conformational changes in prestin generate changes in the length of OHCs. A loss of prestin function is reported to induce severe auditory deficiencies, suggesting prestin-dependent changes of OHC length may be at least a part of cochlear amplification. Here we expressed the recombinant FLAG-fused prestin proteins in Sf9 cells and purified to particles of a uniform size in EM. The square-shaped top view of purified prestin, the binding of multiple anti-FLAG antibodies to each prestin particle, the native-PAGE analysis, and the much larger molecular weight obtained from size exclusion chromatography than the estimation for the monomer all support that prestin is a tetramer (Zheng, J., Du, G. G., Anderson, C. T., Keller, J. P., Orem, A., Dallos, P., and Cheatham, M. (2006) J. Biol. Chem. 281, 19916-19924). From negatively stained prestin particles, the three-dimensional structure was reconstructed at 2 nm resolution assuming 4-fold symmetry. Prestin is shown to be a bullet-shaped particle with a large cytoplasmic domain. The surface representation demonstrates indentations on the molecule, and the slice images indicate the inner cavities of sparse densities. The dimensions, 77 x 77 x 115 A, are consistent with the previously reported sizes of motor proteins on the surface of OHCs.

  5. Selective cell-surface labeling of the molecular motor protein prestin

    SciTech Connect

    McGuire, Ryan M.; Silberg, Jonathan J.; Pereira, Fred A.; Raphael, Robert M.

    2011-06-24

    Highlights: {yields} Trafficking to the plasma membrane is required for prestin function. {yields} Biotin acceptor peptide (BAP) was fused to prestin through a transmembrane domain. {yields} BAP-prestin can be metabolically labeled with biotin in HEK293 cells. {yields} Biotin-BAP-prestin allows for selective imaging of fully trafficked prestin. {yields} The biotin-BAP-prestin displays voltage-sensitive activity. -- Abstract: Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity.

  6. Changes in gene expression and hearing thresholds after cochlear implantation

    PubMed Central

    Zhang, Hongzheng; Stark, Gemaine; Reiss, Lina

    2016-01-01

    Hypothesis Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation. Background Between 30–50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes. Methods Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes. Results Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1b, TNFα and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3 and Gjb3). Upregulation of tissue remodeling genes (TGF-β, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds. Conclusion Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss. PMID:25970030

  7. Treating hearing disorders with cell and gene therapy

    NASA Astrophysics Data System (ADS)

    Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

    2014-12-01

    Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

  8. Prestin's role in cochlear frequency tuning and transmission of mechanical responses to neural excitation.

    PubMed

    Mellado Lagarde, Marcia M; Drexl, Markus; Lukashkin, Andrei N; Zuo, Jian; Russell, Ian J

    2008-02-12

    The remarkable power amplifier [1] of the cochlea boosts low-level and compresses high-level vibrations of the basilar membrane (BM) [2]. By contributing maximally at the characteristic frequency (CF) of each point along its length, the amplifier ensures the exquisite sensitivity, narrow frequency tuning, and enormous dynamic range of the mammalian cochlea. The motor protein prestin in the outer hair cell (OHC) lateral membrane is a prime candidate for the cochlear power amplifier [3]. The other contender for this role is the ubiquitous calcium-mediated motility of the hair cell stereocilia, which has been demonstrated in vitro and is based on fast adaptation of the mechanoelectrical transduction channels [4, 5]. Absence of prestin [6] from OHCs results in a 40-60 dB reduction in cochlear neural sensitivity [7]. Here we show that sound-evoked BM vibrations in the high-frequency region of prestin(-/-) mice cochleae are, surprisingly, as sensitive as those of their prestin(+/+) siblings. The BM vibrations of prestin(-/-) mice are, however, broadly tuned to a frequency approximately a half octave below the CF of prestin(+/+) mice at similar BM locations. The peak sensitivity of prestin(+/+) BM tuning curves matches the neural thresholds. In contrast, prestin(-/-) BM tuning curves at their best frequency are >50 dB more sensitive than the neural responses. We propose that the absence of prestin from OHCs, and consequent reduction in stiffness of the cochlea partition, changes the passive impedance of the BM at high frequencies, including the CF. We conclude that prestin influences the cochlear partition's dynamic properties that permit transmission of its vibrations into neural excitation. Prestin is crucial for defining sharp and sensitive cochlear frequency tuning by reducing the sensitivity of the low-frequency tail of the tuning curve, although this necessitates a cochlear amplifier to determine the narrowly tuned tip.

  9. Chloride and Salicylate Influence Prestin-dependent Specific Membrane Capacitance

    PubMed Central

    Santos-Sacchi, Joseph; Song, Lei

    2014-01-01

    The outer hair cell is electromotile, its membrane motor identified as the protein SLC26a5 (prestin). An area motor model, based on two-state Boltzmann statistics, was developed about two decades ago and derives from the observation that outer hair cell surface area is voltage-dependent. Indeed, aside from the nonlinear capacitance imparted by the voltage sensor charge movement of prestin, linear capacitance (Clin) also displays voltage dependence as motors move between expanded and compact states. Naturally, motor surface area changes alter membrane capacitance. Unit linear motor capacitance fluctuation (δCsa) is on the order of 140 zeptofarads. A recent three-state model of prestin provides an alternative view, suggesting that voltage-dependent linear capacitance changes are not real but only apparent because the two component Boltzmann functions shift their midpoint voltages (Vh) in opposite directions during treatment with salicylate, a known competitor of required chloride binding. We show here using manipulations of nonlinear capacitance with both salicylate and chloride that an enhanced area motor model, including augmented δCsa by salicylate, can accurately account for our novel findings. We also show that although the three-state model implicitly avoids measuring voltage-dependent motor capacitance, it registers δCsa effects as a byproduct of its assessment of Clin, which increases during salicylate treatment as motors are locked in the expanded state. The area motor model, in contrast, captures the characteristics of the voltage dependence of δCsa, leading to a better understanding of prestin. PMID:24554714

  10. Continuing to break the sound barrier: genes in hearing.

    PubMed

    Call, Linda M; Morton, Cynthia C

    2002-06-01

    The past year has seen major advances in our understanding of the genes involved in Usher syndrome, as well as the discovery of a myriad of other genes expressed specifically in hair cells. Mouse models continue to be invaluable in illuminating our knowledge of how mutations in genes lead to deafness. The role of mitochondrial genes in the hearing process has also contributed to elucidating the workings of the auditory system.

  11. [Gene therapy for human hearing loss: challenges and promises].

    PubMed

    Meyer, Anaïs; Petit, Christine; Safieddine, Saaid

    2013-10-01

    Thanks to the advances accomplished in human genomics during the last twenty years, major progress has been made towards understanding the pathogenesis of various forms of congenital or acquired deafness. The identification of deafness genes, which are potential therapeutic targets, and generation and functional characterization of murine models for human deafness forms have advanced the knowledge of the molecular physiology of auditory sensory cells. These milestones have opened the way for the development of new therapeutic strategies, alternatives to conventional prostheses, hearing amplification for mild-to-severe hearing loss, or cochlear implantation for severe-to-profound deafness. In this review, we first summarize the progress made over the last decade in using gene therapy and antisense RNA delivery, including the development of new methods for cochlear gene transfer. We then discuss the potential of gene therapy for curing acquired or inherited deafness and the major obstacles that must be overcome before clinical application can be considered.

  12. Cetaceans on a molecular fast track to ultrasonic hearing.

    PubMed

    Liu, Yang; Rossiter, Stephen J; Han, Xiuqun; Cotton, James A; Zhang, Shuyi

    2010-10-26

    The early radiation of cetaceans coincides with the origin of their defining ecological and sensory differences [1, 2]. Toothed whales (Odontoceti) evolved echolocation for hunting 36-34 million years ago, whereas baleen whales (Mysticeti) evolved filter feeding and do not echolocate [2]. Echolocation in toothed whales demands exceptional high-frequency hearing [3], and both echolocation and ultrasonic hearing have also evolved independently in bats [4, 5]. The motor protein Prestin that drives the electromotility of the outer hair cells (OHCs) is likely to be especially important in ultrasonic hearing, because it is the vibratory response of OHC to incoming sound waves that confers the enhanced sensitivity and selectivity of the mammalian auditory system [6, 7]. Prestin underwent adaptive change early in mammal evolution [8] and also shows sequence convergence between bats and dolphins [9, 10], as well as within bats [11]. Focusing on whales, we show for the first time that the extent of protein evolution in Prestin can be linked directly to the evolution of high-frequency hearing. Moreover, we find that independent cases of sequence convergence in mammals have involved numerous identical amino acid site replacements. Our findings shed new light on the importance of Prestin in the evolution of mammalian hearing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Sensitivity of Prestin-Based Membrane Motor to Membrane Thickness

    PubMed Central

    Fang, Jie; Izumi, Chisako; Iwasa, Kuni H.

    2010-01-01

    Abstract Prestin is the membrane protein in outer hair cells that harnesses electrical energy by changing its membrane area in response to changes in the membrane potential. To examine the effect of membrane thickness on this protein, phosphatidylcholine (PC) with various acyl-chain lengths were incorporated into the plasma membrane by using γ-cyclodextrin. Incorporation of short chain PCs increased the linear capacitance and positively shifted the voltage dependence of prestin, up to 120 mV, in cultured cells. PCs with long acyl chains had the opposite effects. Because the linear capacitance is inversely related to the membrane thickness, these voltage shifts are attributable to membrane thickness. The corresponding voltage shifts of electromotility were observed in outer hair cells. These results demonstrate that electromotility is extremely sensitive to the thickness of the plasma membrane, presumably involving hydrophobic mismatch. These observations indicate that the extended state of the motor molecule, which is associated with the elongation of outer hair cells, has a conformation with a shorter hydrophobic height in the lipid bilayer. PMID:20550895

  14. Intracellular calcium affects prestin's voltage operating point indirectly via turgor-induced membrane tension

    NASA Astrophysics Data System (ADS)

    Song, Lei; Santos-Sacchi, Joseph

    2015-12-01

    Recent identification of a calmodulin binding site within prestin's C-terminus indicates that calcium can significantly alter prestin's operating voltage range as gauged by the Boltzmann parameter Vh (Keller et al., J. Neuroscience, 2014). We reasoned that those experiments may have identified the molecular substrate for the protein's tension sensitivity. In an effort to understand how this may happen, we evaluated the effects of turgor pressure on such shifts produced by calcium. We find that the shifts are induced by calcium's ability to reduce turgor pressure during whole cell voltage clamp recording. Clamping turgor pressure to 1kPa, the cell's normal intracellular pressure, completely counters the calcium effect. Furthermore, following unrestrained shifts, collapsing the cells abolishes induced shifts. We conclude that calcium does not work by direct action on prestin's conformational state. The possibility remains that calcium interaction with prestin alters water movements within the cell, possibly via its anion transport function.

  15. Genomic advances for gene discovery in hereditary hearing loss.

    PubMed

    Avraham, Karen B; Kanaan, Moien

    2012-09-07

    High-throughput sequencing is changing the face of genetic diagnosis and counseling. While in the past, it would take on average 1 to 5 years to identify a mutation leading to deafness, today, the genetic basis for deafness can be determined within months in a child or adult with inherited hearing loss. Obstacles and challenges still remain, but the field is changing at a dramatic rate, making gene discovery a much easier and more efficient task than in the past.

  16. Mammalian prestin is a weak Cl⁻/HCO₃⁻ electrogenic antiporter.

    PubMed

    Mistrík, P; Daudet, N; Morandell, K; Ashmore, J F

    2012-11-15

    The lateral membrane of mammalian cochlear outer hair cells contains prestin, a protein which can act as a fast voltage-driven actuator responsible for electromotility and enhanced sensitivity to sound. The protein belongs to the SLC26 family of transporters whose members are characterised as able to exchange halides for SO(4)(2-) or HCO(3)(-) yet previous analyses of mammalian prestin have suggested that such exchange functions were minimal. Here anion transport is investigated both in guinea-pig outer hair cells (OHCs) and in an expression system where we employ a sensitive intracellular pH (pH(i)) probe, pHluorin, to report HCO(3)(-) transport and to monitor the small pH(i) changes observable in the cells. In the presence of extracellular HCO(3)(-), pH(i) recovered from an acid load 4 times faster in prestin-transfected cells. The acceleration required a chloride gradient established by reducing extracellular chloride to 2 mm. Similar results were also shown using BCECF as an alternative pH(i) sensor, but with recovery only found in those cells expressing prestin. Simultaneous electrophysiological recording of the transfected cells during bicarbonate exposure produced a shift in the reversal potential to more negative potentials, consistent with electrogenic transport. These data therefore suggest that prestin can act as a weak Cl(-)/HCO(3)(-) antiporter and it is proposed that, in addition to participating in wide band cochlear sound amplification, prestin may also be involved in the slow time scale (>10 s) phenomena where changes in cell stiffness and internal pressure have been implicated. The results show the importance of considering the effects of the endogenous bicarbonate buffering system in evaluating the function of prestin in cochlear outer hair cells.

  17. Hearing

    ERIC Educational Resources Information Center

    Koehlinger, Keegan M.; Van Horne, Amanda J. Owen; Moeller, Mary Pat

    2013-01-01

    Purpose: Spoken language skills of 3- and 6-year-old children who are hard of hearing (HH) were compared with those of children with normal hearing (NH). Method: Language skills were measured via mean length of utterance in words (MLUw) and percent correct use of finite verb morphology in obligatory contexts based on spontaneous conversational…

  18. Hearing

    ERIC Educational Resources Information Center

    Koehlinger, Keegan M.; Van Horne, Amanda J. Owen; Moeller, Mary Pat

    2013-01-01

    Purpose: Spoken language skills of 3- and 6-year-old children who are hard of hearing (HH) were compared with those of children with normal hearing (NH). Method: Language skills were measured via mean length of utterance in words (MLUw) and percent correct use of finite verb morphology in obligatory contexts based on spontaneous conversational…

  19. Hereditary hearing loss and deafness genes in Japan.

    PubMed

    Ito, Taku; Noguchi, Yoshihiro; Yashima, Takatoshi; Ohno, Kazuchika; Kitamura, Ken

    2010-03-01

    Hearing loss (HL) is the most common sensory impairment occurring at birth in developed countries. Epidemiological data show that more than one child in 1000 is born with HL, while more than 50% of prelingual HL cases are found to be hereditary. Approximately 70% of hereditary HL is nonsyndromic and subdivided to autosomal dominant (20%), autosomal recessive (75%), X-linked HL (1%), and maternally-inherited HL associated with the mitochondrial DNA mutation. More than 10 deafness genes have been reported to be responsible for nonsyndromic hereditary HL in Japan. Among them, the most prevalent causative genes, GJB2 and the mitochondrial DNA 12SrRNA are introduced. In addition, this study also refers to the specific genes responsible for the unique audiogram, mainly WFS1. Finally, the genes related to the enlargement of vestibular aqueduct of inner ear abnormality, SLC26A4, EYA1 and SIX1 are discussed. The clinical and genetic findings associated with these disorders including the results of a recent study are reviewed.

  20. Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters

    PubMed Central

    Gorbunov, Dmitry; Sturlese, Mattia; Nies, Florian; Kluge, Murielle; Bellanda, Massimo; Battistutta, Roberto; Oliver, Dominik

    2014-01-01

    Prestin (SLC26A5) is a member of the SLC26/SulP anion transporter family. Its unique quasi-piezoelectric mechanical activity generates fast cellular motility of cochlear outer hair cells, a key process underlying active amplification in the mammalian ear. Despite its established physiological role, it is essentially unknown how prestin can generate mechanical force, since structural information on SLC26/SulP proteins is lacking. Here we derive a structural model of prestin and related transporters by combining homology modelling, MD simulations and cysteine accessibility scanning. Prestin’s transmembrane core region is organized in a 7+7 inverted repeat architecture. The model suggests a central cavity as the substrate-binding site located midway of the anion permeation pathway, which is supported by experimental solute accessibility and mutational analysis. Anion binding to this site also controls the electromotile activity of prestin. The combined structural and functional data provide a framework for understanding electromotility and anion transport by SLC26 transporters. PMID:24710176

  1. Chloride and salicylate influence prestin-dependent specific membrane capacitance: support for the area motor model.

    PubMed

    Santos-Sacchi, Joseph; Song, Lei

    2014-04-11

    The outer hair cell is electromotile, its membrane motor identified as the protein SLC26a5 (prestin). An area motor model, based on two-state Boltzmann statistics, was developed about two decades ago and derives from the observation that outer hair cell surface area is voltage-dependent. Indeed, aside from the nonlinear capacitance imparted by the voltage sensor charge movement of prestin, linear capacitance (Clin) also displays voltage dependence as motors move between expanded and compact states. Naturally, motor surface area changes alter membrane capacitance. Unit linear motor capacitance fluctuation (δCsa) is on the order of 140 zeptofarads. A recent three-state model of prestin provides an alternative view, suggesting that voltage-dependent linear capacitance changes are not real but only apparent because the two component Boltzmann functions shift their midpoint voltages (Vh) in opposite directions during treatment with salicylate, a known competitor of required chloride binding. We show here using manipulations of nonlinear capacitance with both salicylate and chloride that an enhanced area motor model, including augmented δCsa by salicylate, can accurately account for our novel findings. We also show that although the three-state model implicitly avoids measuring voltage-dependent motor capacitance, it registers δCsa effects as a byproduct of its assessment of Clin, which increases during salicylate treatment as motors are locked in the expanded state. The area motor model, in contrast, captures the characteristics of the voltage dependence of δCsa, leading to a better understanding of prestin.

  2. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    PubMed

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

  3. An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population.

    PubMed

    Ghasemnejad, Tohid; Shekari Khaniani, Mahmoud; Zarei, Fatemeh; Farbodnia, Mina; Mansoori Derakhshan, Sima

    2017-06-01

    Autosomal-recessive genes are responsible for about 80% of the hereditary non-syndromic hearing loss (NSHL) cases. In Iran, due to consanguineous marriages, NSHL is the second most frequent disability after intellectual disability, occurring one in 16 individuals. Enormous heterogeneity in the genetic pathology of hearing loss causes a major challenge in identification of responsible genes. In Iran, GJB2 is responsible for the most cases of pre-lingual and non-syndromic hearing loss (with frequency of 16.7%) which followed by other genes with lower frequency. Although several studies have indicated that a large proportion of both syndromic and non-syndromic hearing loss in Iranian populations are caused by defects in just a few genes, new detection strategies such as NGS (Next-generation sequencing) have increased the spectrum of responsible mutations. However, by applying this technique in Iran patients screening, the role of lots of novel related genes have been reported. In this review, we aim to describe function of these genes and their contribution to non-syndromic genetic hearing loss in Iranian population and we classify the genes by their functions. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Probing conformational changes of prestin with thiol-reactive optical switches.

    PubMed

    Fang, Jie; Sakata, Tomoyo; Marriott, Gerard; Iwasa, Kuni H

    2008-09-15

    Thiol-reactive optical switch probes were used to examine conformational changes of prestin-based membrane motor. Because this motor is based on mechanoelectric coupling similar to piezoelectricity, the motile activity can be monitored by charge movements across the plasma membrane, which appears as nonlinear capacitance. When the plasma membrane is conjugated with the probes, optically induced spiro-merocyanine transition positively shifted nonlinear capacitance of outer hair cells and prestin-transfected cells by approximately 10 mV. These shifts were reversible and were eliminated by pretreatment with iodoacetamide. However, they were little affected by pretreatment with biotin maleimide, which cannot reach the cytoplasmic surface. Our results showed that merocyanine states, with a larger dipole moment, interact with the motor's extended conformation stronger than with the compact conformation by 1.6 x 10(-21) J/molecule. The interaction sites are near the cytoplasmic side of the motor protein.

  5. Probing Conformational Changes of Prestin with Thiol-Reactive Optical Switches

    PubMed Central

    Fang, Jie; Sakata, Tomoyo; Marriott, Gerard; Iwasa, Kuni H.

    2008-01-01

    Thiol-reactive optical switch probes were used to examine conformational changes of prestin-based membrane motor. Because this motor is based on mechanoelectric coupling similar to piezoelectricity, the motile activity can be monitored by charge movements across the plasma membrane, which appears as nonlinear capacitance. When the plasma membrane is conjugated with the probes, optically induced spiro-merocyanine transition positively shifted nonlinear capacitance of outer hair cells and prestin-transfected cells by ∼10 mV. These shifts were reversible and were eliminated by pretreatment with iodoacetamide. However, they were little affected by pretreatment with biotin maleimide, which cannot reach the cytoplasmic surface. Our results showed that merocyanine states, with a larger dipole moment, interact with the motor's extended conformation stronger than with the compact conformation by 1.6 × 10−21 J/molecule. The interaction sites are near the cytoplasmic side of the motor protein. PMID:18556757

  6. Impact of gene patents and licensing practices on access to genetic testing for hearing loss.

    PubMed

    Chandrasekharan, Subhashini; Fiffer, Melissa

    2010-04-01

    Genetic testing for heritable hearing loss involves a mix of patented and unpatented genes, mutations and testing methods. More than half of all hearing loss is linked to inherited mutations, and five genes are most commonly tested for in the United States. There are no patents on three of these genes, but Athena Diagnostics holds exclusive licenses to test for a common mutation in the GJB2 gene associated with about 50% of all cases as well as mutations in the MTRNR1 gene. This fragmented intellectual property landscape made hearing loss a useful case study to assess whether patent rights in genetic testing can proliferate or overlap, and whether it is possible to gather the rights necessary to perform testing. Testing for hearing loss is widely available, primarily from academic medical centers. Based on literature reviews and interviews with researchers, research on the genetics of hearing loss has generally not been impeded by patents. There is no consistent evidence of a premium in testing prices attributable to patent status. Athena Diagnostics has, however, used its intellectual property to discourage other providers from offering some tests. There is no definitive answer about the suitability of current patenting and licensing of commonly tested genes because of continuing legal uncertainty about the extent of enforcement of patent rights. Clinicians have also expressed concerns that multiplex tests will be difficult to develop because of overlapping intellectual property and conflict with Athena's sole provider business model.

  7. Prevalence of mitochondrial gene mutations among hearing impaired patients

    PubMed Central

    Usami, S.; Abe, S.; Akita, J.; Namba, A.; Shinkawa, H.; Ishii, M.; Iwasaki, S.; Hoshino, T.; Ito, J.; Doi, K.; Kubo, T.; Nakagawa, T.; Komiyama, S.; Tono, T.; Komune, S.

    2000-01-01

    The frequency of three mitochondrial point mutations, 1555A→G, 3243A→G, and 7445A→G, known to be associated with hearing impairment, was examined using restriction fragment length polymorphism (RFLP) analysis in two Japanese groups: (1) 319 unrelated SNHL outpatients (including 21 with aminoglycoside antibiotic injection history), and (2) 140 cochlear implantation patients (including 22 with aminoglycoside induced hearing loss). Approximately 3% of the outpatients and 10% of the cochlear implantation patients had the 1555A→G mutation. The frequency was higher in the patients with a history of aminoglycoside injection (outpatient group 33%, cochlear implantation group 59%). One outpatient (0.314%) had the 3243A→G mutation, but no outpatients had the 7445A→G mutation and neither were found in the cochlear implantation group. The significance of the 1555A→G mutation, the most prevalent mitochondrial mutation found in this study of a hearing impaired population in Japan, among subjects with specific backgrounds, such as aminoglycoside induced hearing loss, is evident.


Keywords: mitochondria; point mutation; hearing impairment; frequencies PMID:10633132

  8. Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness.

    PubMed

    Iizuka, Takashi; Kamiya, Kazusaku; Gotoh, Satoru; Sugitani, Yoshinobu; Suzuki, Masaaki; Noda, Tetsuo; Minowa, Osamu; Ikeda, Katsuhisa

    2015-07-01

    Hearing loss is the most widespread sensory disorder, with an incidence of congenital genetic deafness of 1 in 1600 children. For many ethnic populations, the most prevalent form of genetic deafness is caused by recessive mutations in the gene gap junction protein, beta 2, 26 kDa (GJB2), which is also known as connexin 26 (Cx26). Despite this knowledge, existing treatment strategies do not completely recover speech perception. Here we used a gene delivery system to rescue hearing in a mouse model of Gjb2 deletion. Mice lacking Cx26 are characterized by profound deafness from birth and improper development of cochlear cells. Cochlear delivery of Gjb2 using an adeno-associated virus significantly improved the auditory responses and development of the cochlear structure. Using gene replacement to restore hearing in a new mouse model of Gjb2-related deafness may lead to the development of therapies for human hereditary deafness.

  9. A Novel Nonsense Mutation of POU4F3 Gene Causes Autosomal Dominant Hearing Loss

    PubMed Central

    Zhang, Chi; Wang, Mingming; Zhang, Fengguo; Zhou, Yicui; Li, Jianfeng; Zheng, Qingyin; Bai, Xiaohui

    2016-01-01

    POU4F3 gene encodes a transcription factor which plays an essential role in the maturation and maintenance of hair cells in cochlea and vestibular system. Several mutations of POU4F3 have been reported to cause autosomal dominant nonsyndromic hearing loss in recent years. In this study, we describe a pathogenic nonsense mutation located in POU4F3 in a four-generation Chinese family. Target region capture sequencing was performed to search for the candidate mutations from 81 genes related to nonsyndromic hearing loss in this family. A novel nonsense mutation of POU4F3, c.337C>T (p. Gln113⁎), was identified in a Chinese family characterized by late-onset progressive nonsyndromic hearing loss. The novel mutation cosegregated with hearing loss in this family and was absent in 200 ethnicity-matched controls. The mutation led to a stop codon and thus a truncated protein with no functional domains remained. Transient transfection and immunofluorescence assay revealed that the subcellular localization of the truncated protein differed markedly from normal protein, which could be the underlying reason for complete loss of its normal function. Here, we report the first nonsense mutation of POU4F3 associated with progressive hearing loss and explored the possible underlying mechanism. Routine examination of POU4F3 is necessary for the genetic diagnosis of hereditary hearing loss in the future. PMID:27999687

  10. Mutations in LOXHD1 gene cause various types and severities of hearing loss

    PubMed Central

    Mori, Kentaro; Moteki, Hideaki; Kobayashi, Yumiko; Azaiez, Hela; Booth, Kevin T; Nishio, Shin-ya; Sato, Hiroaki; Smith, Richard J H; Usami, Shin-ichi

    2015-01-01

    Objective We present two families that were identified with novel mutations in LOXHD1, as a cause of non-progressive hearing loss. Methods One thousand three hundred fourteen (1,314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results Two patients in one family affected with homozygous mutation; c.879+1G>A in LOXHD1, showed profound congenital hearing loss, whereas two patients in the other family with compound heterozygous mutations; c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X) showed moderate to severe hearing loss. Conclusion Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences of phenotypes in each patient might be the result of the nature of the mutations, or the location at the gene, or be influenced by genetic modifier. PMID:25792669

  11. Have you heard? Viral-mediated gene therapy restores hearing.

    PubMed

    Martin, Donna M; Raphael, Yehoash

    2012-07-26

    Genetic loss of VGLUT3 in cochlear inner hair cells results in profound deafness. In this issue of Neuron, Akil et al. (2012) show that AAV-mediated introduction of wild-type VGLUT3 in the genetically deaf mouse cochlea results in significantly improved hearing.

  12. Genetic analysis of TMPRSS3 gene in the Korean population with autosomal recessive nonsyndromic hearing loss.

    PubMed

    Lee, Jinwook; Baek, Jeong-In; Choi, Jae Young; Kim, Un-Kyung; Lee, Sang-Heun; Lee, Kyu-Yup

    2013-12-15

    The TMPRSS3 gene (DFNB8/10), which encodes a transmembrane serine protease, is a common hearing loss gene in several populations. Accurate functions of TMPRSS3 in the hearing pathway are still unknown, but TMPRSS3 has been reported to play a crucial role in inner ear development or maintenance. To date, 16 pathogenic mutations have been identified in many countries, but no mutational studies of the TMPRSS3 gene have been conducted in the Korean hearing loss population. In this study, we performed genetic analysis of TMPRSS3 in 40 unrelated Korean patients with autosomal recessive hearing loss to identify the aspect and frequency of TMPRSS3 gene mutations in the Korean population. A total of 22 variations were detected, including a novel variant (p.V291L) and a previously reported pathogenic mutation (p.A306T). The p.A306T mutation which has been detected in only compound heterozygous state in previous studies was identified in homozygous state for the first time in this study. Moreover, the clinical evaluation identified bilateral dilated vestibules in the patient with p.A306T mutation, and it suggested that p.A306T mutation of the TMPRSS3 gene might be associated with vestibular anomalies. In conclusion, this study investigated that only 2.5% of patients with autosomal recessive hearing loss were related to TMPRSS3 mutations suggesting low prevalence of TMPRSS3 gene in Korean hearing loss population. Also, it will provide the information of genotype-phenotype correlation to understand definite role of TMPRSS3 in the auditory system.

  13. A gene for autosomal dominant hearing loss on the short arm of chromosome 1

    SciTech Connect

    Van Camp, G.; Coucke, P.; Willems, P.J.

    1994-09-01

    Hearing loss is the most common form of sensory impairment and many cases are attributable to genetic causes. The genetic defects underlying several syndromic forms of deafness have been identified, but little is known about the causes of non-syndromic hereditary deafness which accounts for the majority of inherited hearing loss. We report here a large Indonesian family with non-syndromal postlingual hearing loss starting in the high frequencies and showing autosomal dominant inheritance. To locate the gene responsible for the hearing loss in this family, we performed a genome search by genetic linkage analysis with microsatellite markers distributed over the whole genome. We have mapped the gene causing deafness in an extended Indonesian family to chromosome 1p with a multipoint lod score higher than 7. Two other smaller families, showing a similar hereditary hearing loss, were also tested for linkage with chromosome 1p. One family originating from the U.S. was linked to this new locus with a multipoint lod score exceeding 5. In another family from the Netherlands this locus was excluded. The flanking markers D1S255 and D1S211 define a region of 6 cM on chromosome 1p which is likely to contain the deafness gene present in the Indonesian and American family.

  14. Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea

    PubMed Central

    Tadros, Sherif F.; D’Souza, Mary; Zhu, Xiaoxia

    2010-01-01

    To understand possible causative roles of apoptosis gene regulation in age-related hearing loss (presbycusis), apoptotic gene expression patterns in the CBA mouse cochlea of four different age and hearing loss groups were compared, using GeneChip and real-time (qPCR) microarrays. GeneChip transcriptional expression patterns of 318 apoptosis-related genes were analyzed. Thirty eight probes (35 genes) showed significant differences in expression. The significant gene families include Caspases, B-cell leukemia/lymphoma2 family, P53, Cal-pains, Mitogen activated protein kinase family, Jun oncogene, Nuclear factor of kappa light chain gene enhancer in B-cells inhibitor-related and tumor necrosis factor-related genes. The GeneChip results of 31 genes were validated using the new TaqMan® Low Density Array (TLDA). Eight genes showed highly correlated results with the GeneChip data. These genes are: activating transcription factor3, B-cell leukemia/lymphoma2, Bcl2-like1, caspase4 apoptosis-related cysteine protease 4, Calpain2, dual specificity phosphatase9, tumor necrosis factor receptor superfamily member12a, and Tumor necrosis factor superfamily member13b, suggesting they may play critical roles in inner ear aging. PMID:18839313

  15. Expression and replication studies to identify new candidate genes involved in normal hearing function.

    PubMed

    Girotto, Giorgia; Vuckovic, Dragana; Buniello, Annalisa; Lorente-Cánovas, Beatriz; Lewis, Morag; Gasparini, Paolo; Steel, Karen P

    2014-01-01

    Considerable progress has been made in identifying deafness genes, but still little is known about the genetic basis of normal variation in hearing function. We recently carried out a Genome Wide Association Study (GWAS) of quantitative hearing traits in southern European populations and found several SNPs with suggestive but none with significant association. In the current study, we followed up these SNPs to investigate which of them might show a genuine association with auditory function using alternative approaches. Firstly, we generated a shortlist of 19 genes from the published GWAS results. Secondly, we carried out immunocytochemistry to examine expression of these 19 genes in the mouse inner ear. Twelve of them showed distinctive cochlear expression patterns. Four showed expression restricted to sensory hair cells (Csmd1, Arsg, Slc16a6 and Gabrg3), one only in marginal cells of the stria vascularis (Dclk1) while the others (Ptprd, Grm8, GlyBP, Evi5, Rimbp2, Ank2, Cdh13) in multiple cochlear cell types. In the third step, we tested these 12 genes for replication of association in an independent set of samples from the Caucasus and Central Asia. Nine out of them showed nominally significant association (p<0.05). In particular, 4 were replicated at the same SNP and with the same effect direction while the remaining 5 showed a significant association in a gene-based test. Finally, to look for genotype-phenotype relationship, the audiometric profiles of the three genotypes of the most strongly associated gene variants were analyzed. Seven out of the 9 replicated genes (CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1) showed an audiometric pattern with differences between different genotypes further supporting their role in hearing function. These data demonstrate the usefulness of this multistep approach in providing new insights into the molecular basis of hearing and may suggest new targets for treatment and prevention of hearing impairment.

  16. [Combined hearing and deafness gene mutation screening of 11,046 Chinese newborns].

    PubMed

    Sun, Xuejing; Xi, Zuoming; Zhang, Jing; Liu, Baoyan; Xing, Xinli; Huang, Xin; Zhao, Qing

    2015-12-01

    To evaluate the efficacy of combined newborn hearing screening and deafness-related mutation screening. Eleven thousand and forty-six newborn babies were screened with otoacoustic emission, automatic auditory brainstem response and genetic testing using a standard protocol. Common mutations of three deafness-related genes have included GJB2 (c.235delC, c.299-300delAT), mtDNA 12srRNA (c.1494C>T, c.1555A>G) and SLC26A4 (c.2168A>G, c.IVS7-2A>G). The detection rate for hearing loss in the first-step screening was 0.81% (90/11,046). 513 individuals were found to carry one or two mutant alleles, which gave a carrier rate of 4.64% (513/11,046). Five hundred and eighty-four newborns were positive for hearing screening and genetic screening. Among these, 19 have failed both tests, 71 have failed hearing screening, and 494 have failed genetic screening. The combined hearing and genetic screening has given a positive rate of 5.29%. Neither hearing screening nor genetic screening is sufficient to identify individuals susceptible to auditory disorders. Combined used of these methods can improve the rate of detection.

  17. Expression of toll-like receptor genes in leukocytes of patients with sudden sensorineural hearing loss.

    PubMed

    Yang, Chao-Hui; Hwang, Chung-Feng; Yang, Ming-Yu; Lin, Pai-Mei; Chuang, Jiin-Haur

    2015-12-01

    Sudden sensorineural hearing loss (SNNHL) is a disease entity that could be caused by multiple etiologies in which the innate immunity status of the patients might be involved. The aim of this study is to investigate the expression of Toll-like receptor (TLR) genes in peripheral blood leukocytes of SNNHL patients. Basic research. We examined the expression of six TLR genes in the peripheral blood leukocytes of SNNHL patients and normal controls using real-time quantitative reverse transcriptase-polymerase chain reaction. We found significantly higher expression of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 genes in SNNHL patients as compared with normal controls (P < 0.05). Higher expression of the TLR2 gene was found in patients with profound hearing loss compared with those with less severe hearing loss (P < 0.05). The result was validated by the positively stained leukocytes for TLR2 protein in SNNHL patients using the immunocytochemical study. In addition, the percentage of CD14(+) monocytes expressing TLR2 in SNNHL patients was higher than in normal controls assessed by flow cytometry and significantly correlated with the hearing thresholds of the affected ear (P < 0.05). Our study implies a role for TLRs in SNNHL. The expression of TLR2 in particular correlates with the severity of the disease. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study.

    PubMed

    Fisher, Diana E; Li, Chuan-Ming; Hoffman, Howard J; Chiu, May S; Themann, Christa L; Petersen, Hannes; Jonsson, Palmi V; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

    2015-01-01

    We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Population-based cohort study. A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women.

  19. Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study

    PubMed Central

    Fisher, Diana E.; Li, Chuan-Ming; Hoffman, Howard J.; Chiu, May S.; Themann, Christa L.; Petersen, Hannes; Jonsson, Palmi V.; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J.; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

    2015-01-01

    Objective We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Design Population-based cohort study. Study sample A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Results Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Conclusions Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women. PMID:25816699

  20. A rapid method for simultaneous screening of multi-gene mutations associated with hearing loss in the Korean population.

    PubMed

    Sagong, Borum; Baek, Jeong-In; Oh, Se-Kyung; Na, Kyung Jin; Bae, Jae Woong; Choi, Soo Young; Jeong, Ji Yun; Choi, Jae Young; Lee, Sang-Heun; Lee, Kyu-Yup; Kim, Un-Kyung

    2013-01-01

    Hearing loss (HL) is a congenital disease with a high prevalence, and patients with hearing loss need early diagnosis for treatment and prevention. The GJB2, MT-RNR1, and SLC26A4 genes have been reported as common causative genes of hearing loss in the Korean population and some mutations of these genes are the most common mutations associated with hearing loss. Accordingly, we developed a method for the simultaneous detection of seven mutations (c.235delC of GJB2, c.439A>G, c.919-2A>G, c.1149+3A>G, c.1229C>T, c.2168A>G of SLC26A4, and m.1555A>G of the MT-RNR1 gene) using multiplex SNaPshot minisequencing to enable rapid diagnosis of hereditary hearing loss. This method was confirmed in patients with hearing loss and used for genetic diagnosis of controls with normal hearing and neonates. We found that 4.06% of individuals with normal hearing and 4.32% of neonates were heterozygous carriers. In addition, we detected that an individual is heterozygous for two different mutations of GJB2 and SLC26A4 gene, respectively and one normal hearing showing the heteroplasmy of m.1555A>G. These genotypes corresponded to those determined by direct sequencing. Overall, we successfully developed a robust and cost-effective diagnosis method that detects common causative mutations of hearing loss in the Korean population. This method will be possible to detect up to 40% causative mutations associated with prelingual HL in the Korean population and serve as a useful genetic technique for diagnosis of hearing loss for patients, carriers, neonates, and fetuses.

  1. Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study

    PubMed Central

    2011-01-01

    Background Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI), however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular functioning. Despite the extensive investigations regarding the roles of folate metabolism related gene polymorphisms in the pathophysiology of complex diseases, such as cancer, cardio-cerebrovascular disease, and atherosclerosis, little is known about the association with ARHI. The aim of this study is to investigate the effects of the methionine synthase (MTR) A2756G and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms on the risk of hearing impairment in middle-aged and elderly Japanese. Methods Data were collected from community-dwelling Japanese adults aged 40-84 years who participated in the Longitudinal Study of Aging biennially between 1997 and 2008. We analyzed cumulative data (5,167 samples in accumulated total) using generalized estimating equations. Results The MTHFR 677T allele was significantly associated with a reduced risk of hearing impairment only when the subjects were wild-type homozygotes for MTR A2756G. The per-T allele odds ratio of MTHFR for the risk of developing hearing impairment was 0.7609 (95% CI: 0.6178-0.9372) in the MTR AA genotype. In addition, a subgroup analysis demonstrated that the favorable effect of the MTHFR 677T allele on the risk of developing hearing impairment was independent of folate and homocysteine level, whereas plasma total homocysteine level was independently associated with an increased risk of developing hearing impairment. The interactive effect of gene polymorphisms associated with folate metabolism may modify the risk of developing hearing impairment after middle age. These results contribute to the elucidation of the causes of ARHI. Conclusions The present study has found that the MTHFR 677T allele has a favorable effect on a

  2. Salt-inducible kinase 3, SIK3, is a new gene associated with hearing

    PubMed Central

    Wolber, Lisa E.; Girotto, Giorgia; Buniello, Annalisa; Vuckovic, Dragana; Pirastu, Nicola; Lorente-Cánovas, Beatriz; Rudan, Igor; Hayward, Caroline; Polasek, Ozren; Ciullo, Marina; Mangino, Massimo; Steves, Claire; Concas, Maria Pina; Cocca, Massilimiliano; Spector, Tim D.; Gasparini, Paolo; Steel, Karen P.; Williams, Frances M.K.

    2014-01-01

    Hearing function is known to be heritable, but few significant and reproducible associations of genetic variants have been identified to date in the adult population. In this study, genome-wide association results of hearing function from the G-EAR consortium and TwinsUK were used for meta-analysis. Hearing ability in eight population samples of Northern and Southern European ancestry (n = 4591) and the Silk Road (n = 348) was measured using pure-tone audiometry and summarized using principal component (PC) analysis. Genome-wide association analyses for PC1–3 were conducted separately in each sample assuming an additive model adjusted for age, sex and relatedness of subjects. Meta-analysis was performed using 2.3 million single-nucleotide polymorphisms (SNPs) tested against each of the three PCs of hearing ability in 4939 individuals. A single SNP lying in intron 6 of the salt-inducible kinase 3 (SIK3) gene was found to be associated with hearing PC2 (P = 3.7×10−8) and further supported by whole-genome sequence in a subset. To determine the relevance of this gene in the ear, expression of the Sik3 protein was studied in mouse cochlea of different ages. Sik3 was expressed in murine hair cells during early development and in cells of the spiral ganglion during early development and adulthood. Our results suggest a developmental role of Sik3 in hearing and may be required for the maintenance of adult auditory function. PMID:25060954

  3. Treating Combat Hearing Loss with Atoh1 Gene Therapy

    DTIC Science & Technology

    2011-10-01

    using microarray profiling, as many of the genes up-regulated are involved in cell death, not in hair cells themselves. This deliverable could not...in the Atoh1 mutant cochlea. Deliverable 3: The data collected from our microarray and deep sequencing work described above gives us a list of all...genes expressed preferentially in hair cells. However, it does not tell us which of these genes are directly regulated by the Atoh1 transcription

  4. Rare compound heterozygosity involving dominant and recessive mutations of GJB2 gene in an assortative mating hearing impaired Indian family.

    PubMed

    Pavithra, Amritkumar; Chandru, Jayasankaran; Jeffrey, Justin Margret; Karthikeyen, N P; Srisailapathy, C R Srikumari

    2017-01-01

    Connexin 26 (Cx-26), a gap junction protein coded by GJB2 gene, plays a very important role in recycling of potassium ions, one of the vital steps in the mechanotransduction process of hearing. Mutations in the GJB2 gene have been associated with both autosomal recessive as well as dominant nonsyndromic hearing loss. As Cx-26 is linked with skin homeostasis, mutations in this gene are sometimes associated with syndromic forms of hearing loss showing skin anomalies. We report here a non consanguineous assortatively mating hearing impaired family with one of the hearing impaired partners, their hearing impaired sibling and hearing impaired offspring showing compound heterozygosity in the GJB2 gene, involving a dominant mutation p.R184Q and two recessive mutations p.Q124X and c.IVS 1+1G>A in a unique triallelic combination. To the best of our knowledge, this is the first report from India on p.R184Q mutation in the GJB2 gene associated with rare compound heterozygosity showing nonsyndromic presentation.

  5. [Hereditary sensorineural hearing impairment and macrothrombocytopenia: a rare MYH9 gene mutation].

    PubMed

    Böttcher, A; Knecht, R; Busch, C-J; Lörincz, B B; Dalchow, C V

    2013-02-01

    We report on a rare case of an exon 16 mutation of the MYH9 gene in a 23-year-old woman. This gene encodes for non-muscular myosin IIA, which acts as a cytoskeletal contractile protein in diverse cell types. This disorder led to sensorineural hearing loss, macrothrombocytopenia, and proteinuria. MYH9 gene mutation can lead to diverse organ manifestation like pre-senile cataract or renal failure which are progressive in course. Due to the current lack of causal treatment, diagnostic steps, advice for follow-up examinations and symptomatic therapy approaches are presented.

  6. Does congenital cytomegalovirus infection lead to hearing loss by inducing mutation of the GJB2 gene?

    PubMed

    Li, Lu-Quan; Tan, Jun-Jie; Zhou, Yuan; Yu, Jia-Lin

    2013-08-01

    Congenital cytomegalovirus (CMV) infection and mutation of the gap junction β-2 (GJB2) gene are important causes of sensorineural hearing loss (SNHL). This study aims to determine if congenital CMV infection leads to deafness by inducing GJB2 mutation. GJB2 gene sequencing and auditory brainstem response testing were performed in 159 neonates (63 with and 96 without CMV infection) from August 2008 to August 2011. For neonates with GJB2 mutation, their parents were further screened for GJB2 sequence. The incidence of SNHL was 12.7% in CMV-infected but 0% in uninfected children aged 1-1.5 y (P = 0.000). Similar mutation rates of the GJB2 gene were observed in neonates with or without CMV infection (34.9 vs. 32.3%, respectively, P = 0.734). No significant difference in the mutation rate of GJB2 was found among neonates with CMV infection and SNHL, those with CMV infection and normal hearing, and uninfected newborns with normal hearing (P = 0.438). Mutations 79G>A, 109G>A, 341A>G, and 608T>C were found in neonates with and without CMV infection. All of the above mutations were also found in both or one of the corresponding parents. Congenital CMV infections may cause deafness in neonates, but this might be independent of GJB2 gene mutation.

  7. Sensorineural hearing loss: potential therapies and gene targets for drug development.

    PubMed

    Tang, Louisa S; Montemayor, Celina; Pereira, Fred A

    2006-09-01

    Recent advances in the developmental biology, genetics and cell biology of the inner ear are guiding research to novel therapeutic modalities - a market currently estimated to be at least US Dollars 10 billion. This article highlights prospects to manipulate the mammalian hearing organ with gene and stem cell delivery to the inner ear to protect, repair or regenerate the hair cells, supporting cells and associated nerves.

  8. [The mutation spectrum of the GJB2 gene in Belarussian patients with hearing loss. Results of pilot genetic screening of hearing impairment in newborns].

    PubMed

    Bliznets, E A; Marcul', D N; Khorov, O G; Markova, T G; Poliakov, A V

    2014-02-01

    A total of 111 unrelated probands and their 8 sibs from Grodno oblast (Belarus) with bilateral isolated sensorineural hearing impairment were studied for the presence of mutations in the connexin 26--GJB2gene. Mutations were detected in 51 probands (46% of the sample). A significantly higher frequency of the GJB2gene mutations was observed in familial cases of the disease with the autosomal recessive type of inheritance (in 78% of families). Detected peculiarities of the GJB2 gene mutation spectrum demonstrated that use of the algorithm, which was developed for Russian patients, is optimal for the molecular study of patients from Be- larus. In the sample of patients with hearing loss, the highest (among other similar samples studied in the world) allele frequency of c.313_326de114 mutation (7% out of all pathological GJB2 alleles) was registered; Polish origin of this deletion was suggested. It was demonstrated that detection of the GJB2 gene mutation on only one patient's chromosome is insufficient to confirm a molecular genetic diagnosis of hearing loss of the DFNB1 genetic type (autosomal recessive hearing loss caused by the GJB2 gene mutations). Pilot screening in the presence of GJB2 gene mutations in newborns from Grodno oblast was conducted. The material from 235 children was studied during the screening; nine heterozygous carriers of the mutation were found. The c.35delG mutation was detected in a homozygous state in a single newborn (hearing loss of moderate severity was subsequently audiologically confirmed in this child).

  9. Connexins, hearing and deafness: clinical aspects of mutations in the connexin 26 gene.

    PubMed

    Lefebvre, P P; Van De Water, T R

    2000-04-01

    Congenital deafness is a very frequent disorder occurring in approximately I in 1000 live births. Mutations in GJB2 encoding for gap junction protein connexin-26 (Cx26) have been established as the basis of autosomal recessive non-syndromic hearing loss and proposed in some rare cases of autosomal dominant form of deafness. Connexin are gap-junction proteins which constitute a major system of intercellular communication important in the exchange of electrolytes, second messengers and metabolites. In the inner ear, connexin 26 expression was demonstrated in the stria vascularis, basement membrane, limbus and the spiral prominence of the human cochlea. The loss of connexin 26 in the gap junction complex would expect to disrupt the recycling of potassium from the synapses at the base of hair cells through the supporting cells and fibroblasts of potassium ions back to the high potassium containing endolymph of the cochlear duct and therefore would result in a local intoxication of the Corti s organ by potassium, leading to the hearing loss. The discovery of the genes responsible of hearing loss in particular the identification of mutations in the gene coding for connexin 26 allows to hope some tremendous help in genetic counseling. The possible implication of the mutation of the connexin gene in the pathophysiology of some progressive adult deafness opens new prospects in the fine diagnostic of the ear diseases and eventually may lead to new therapeutic strategies applied to the cochlea.

  10. A Novel Splice-Site Mutation in the GJB2 Gene Causing Mild Postlingual Hearing Impairment

    PubMed Central

    Gandía, Marta; del Castillo, Francisco J.; Rodríguez-Álvarez, Francisco J.; Garrido, Gema; Villamar, Manuela; Calderón, Manuela; Moreno-Pelayo, Miguel A.; Moreno, Felipe; del Castillo, Ignacio

    2013-01-01

    The DFNB1 subtype of autosomal recessive, nonsyndromic hearing impairment, caused by mutations affecting the GJB2 (connection-26) gene, is highly prevalent in most populations worldwide. DFNB1 hearing impairment is mostly severe or profound and usually appears before the acquisition of speech (prelingual onset), though a small number of hypomorphic missense mutations result in mild or moderate deafness of postlingual onset. We identified a novel GJB2 splice-site mutation, c. -22-2A>C, in three siblings with mild postlingual hearing impairment that were compound heterozygous for c. -22-2A>C and c.35delG. Reverse transcriptase-PCR experiments performed on total RNA extracted from saliva samples from one of these siblings confirmed that c. -22-2A>C abolished the acceptor splice site of the single GJB2 intron, resulting in the absence of normally processed transcripts from this allele. However, we did isolate transcripts from the c. -22-2A>C allele that keep an intact GJB2 coding region and that were generated by use of an alternative acceptor splice site previously unknown. The residual expression of wild-type connection-26 encoded by these transcripts probably underlies the mild severity and late onset of the hearing impairment of these subjects. PMID:24039984

  11. Glutamate Transporter Homolog-based Model Predicts That Anion-π Interaction Is the Mechanism for the Voltage-dependent Response of Prestin*

    PubMed Central

    Lovas, Sándor; He, David Z. Z.; Liu, Huizhan; Tang, Jie; Pecka, Jason L.; Hatfield, Marcus P. D.; Beisel, Kirk W.

    2015-01-01

    Prestin is the motor protein of cochlear outer hair cells. Its unique capability to perform direct, rapid, and reciprocal electromechanical conversion depends on membrane potential and interaction with intracellular anions. How prestin senses the voltage change and interacts with anions are still unknown. Our three-dimensional model of prestin using molecular dynamics simulations predicts that prestin contains eight transmembrane-spanning segments and two helical re-entry loops and that tyrosyl residues are the structural specialization of the molecule for the unique function of prestin. Using site-directed mutagenesis and electrophysiological techniques, we confirmed that residues Tyr367, Tyr486, Tyr501, and Tyr508 contribute to anion binding, interacting with intracellular anions through novel anion-π interactions. Such weak interactions, sensitive to voltage and mechanical stimulation, confer prestin with a unique capability to perform electromechanical and mechanoelectric conversions with exquisite sensitivity. This novel mechanism is completely different from all known mechanisms seen in ion channels, transporters, and motor proteins. PMID:26283790

  12. AudioGene: Predicting Hearing Loss Genotypes from Phenotypes to Guide Genetic Screening

    PubMed Central

    Taylor, Kyle R.; DeLuca, Adam P.; Shearer, A. Eliot; Hildebrand, Michael S.; Black-Ziegelbein, E. Ann; Anand, V. Nikhil; Sloan, Christina M.; Eppsteiner, Robert W.; Scheetz, Todd E.; Huygen, Patrick L. M.; Smith, Richard J. H.; Braun, Terry A.; Casavant, Thomas L.

    2013-01-01

    Autosomal Dominant Nonsyndromic Hearing Loss (ADNSHL) is a common and often progressive sensory deficit. ADNSHL displays a high degree of genetic heterogeneity, and varying rates of progression. Accurate, comprehensive and cost-effective genetic testing facilitates genetic counseling and provides valuable prognostic information to affected individuals. In this paper, we describe the algorithm underlying AudioGene, a software system employing machine-learning techniques that utilizes phenotypic information derived from audiograms to predict the genetic cause of hearing loss in persons segregating ADNSHL. Our data show that AudioGene has an accuracy of 68% in predicting the causative gene within its top three predictions, as compared to 44% for a Majority classifier. We also show that AudioGene remains effective for audiograms with high levels of clinical measurement noise. We identify audiometric outliers for each genetic locus and hypothesize that outliers may reflect modifying genetic effects. As personalized genomic medicine becomes more common, AudioGene will be increasingly useful as a phenotypic filter to assess pathogenicity of variants identified by massively parallel sequencing. PMID:23280582

  13. Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea.

    PubMed

    Hosoya, Makoto; Fujioka, Masato; Ogawa, Kaoru; Okano, Hideyuki

    2016-02-26

    Hearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5, and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset.

  14. Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea

    PubMed Central

    Hosoya, Makoto; Fujioka, Masato; Ogawa, Kaoru; Okano, Hideyuki

    2016-01-01

    Hearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5, and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset. PMID:26915689

  15. A novel compound heterozygous mutation (35delG, 363delC) in the Connexin 26 gene causes non-syndromic autosomal recessive hearing loss.

    PubMed

    Onsori, Habib; Rahmati, Mohammad; Fazli, Davood

    2014-01-01

    Mutations in the Connexin 26 (Cx26) gene are a common cause of hereditary hearing loss in different populations. In the present study, an Iranian patient with bilateral hearing loss underwent molecular analysis for the causative mutation. DNA studies were performed for the Cx26 gene by PCR and sequencing methods. We describe a novel compound heterozygous mutation (35delG, 363delC) in the Cx26 gene that is strongly associated with congenital non-syndromic hearing loss (NSHL).

  16. No association between apolipoprotein E or N-acetyltransferase 2 gene polymorphisms and age-related hearing loss.

    PubMed

    Dawes, Piers; Platt, Hazel; Horan, Michael; Ollier, William; Munro, Kevin; Pendleton, Neil; Payton, Antony

    2015-01-01

    Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age-related hearing loss and investigate epistasis between these two genes. Candidate gene association study of a continuous phenotype. We investigated haplotype tagging single nucleotide polymorphisms in the N-acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age-related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N-acetyltransferase 2 gene was obtained from existing genome-wide association study data from the Illumina 610-Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software. No significant associations (P value, > 0.05) were observed between the N-acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N-acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A). We found no evidence to support that either N-acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age-related hearing loss in a cohort of 265 elderly volunteers. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  17. No association between apolipoprotein E or N‐Acetyltransferase 2 gene polymorphisms and age‐related hearing loss

    PubMed Central

    Dawes, Piers; Platt, Hazel; Horan, Michael; Ollier, William; Munro, Kevin; Pendleton, Neil

    2014-01-01

    Objectives/Hypothesis Age‐related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N‐acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age‐related hearing loss and investigate epistasis between these two genes. Study Design Candidate gene association study of a continuous phenotype. Methods We investigated haplotype tagging single nucleotide polymorphisms in the N‐acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age‐related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N‐acetyltransferase 2 gene was obtained from existing genome‐wide association study data from the Illumina 610‐Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software. Results No significant associations (P value, > 0.05) were observed between the N‐acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N‐acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A). Conclusion We found no evidence to support that either N‐acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age‐related hearing loss in a cohort of 265 elderly volunteers. Level of Evidence N/A. Laryngoscope, 125:E33–E38, 2015 PMID:25155015

  18. Identification of a nonsense mutation in the STRC gene in a Korean family with moderate hearing loss.

    PubMed

    Sagong, Borum; Baek, Jeong-In; Bok, Jinwoong; Lee, Kyu-Yup; Kim, Un-Kyung

    2016-01-01

    Hereditary hearing loss is a heterogeneous disorder that results in a common sensorineural disorder. To date, more than 150 loci and 89 genes have been reported for non-syndromic hearing loss. Next generation sequencing has recently been developed as a powerful genetic strategy for identifying pathogenic mutations in heterogeneous disorders with various causative genes. In this study, we performed targeted sequencing to identify the causative mutation in a Korean family that had moderate hearing loss. We targeted 64 genes associated with non-syndromic hearing loss and sorted the homozygous variations according to the autosomal recessive inheritance pattern of the family. Implementing a bioinformatic platform for filtering and detecting variations allowed for the identification of two variations within different genes (c.650G>A in TRIOBP and c.4057C>T in STRC). These variants were selected for further analysis. Among these, c.4057C>T (p.Q1353X) was a divergent sequence variation between the STRC gene and the STRC pseudogene. This was the critical difference that resulted in loss of the protein-coding ability of the pseudogene. Therefore, we hypothesized that the p.Q1353X variation in the STRC gene is the causative mutation for hearing loss. This result suggests that application of targeted sequencing will be valuable for the diagnosis of heterogeneous disorders.

  19. Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss.

    PubMed

    Atik, Tahir; Onay, Huseyin; Aykut, Ayca; Bademci, Guney; Kirazli, Tayfun; Tekin, Mustafa; Ozkinay, Ferda

    2015-01-01

    Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.

  20. Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Atik, Tahir; Onay, Huseyin; Aykut, Ayca; Bademci, Guney; Kirazli, Tayfun; Tekin, Mustafa; Ozkinay, Ferda

    2015-01-01

    Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL. PMID:26561413

  1. Intronic Variants in the NFKB1 Gene May Influence Hearing Forecast in Patients with Unilateral Sensorineural Hearing Loss in Meniere's Disease

    PubMed Central

    Cabrera, Sonia; Sanchez, Elena; Requena, Teresa; Martinez-Bueno, Manuel; Benitez, Jesus; Perez, Nicolas; Trinidad, Gabriel; Soto-Varela, Andrés; Santos-Perez, Sofía; Martin-Sanz, Eduardo; Fraile, Jesus; Perez, Paz; Alarcon-Riquelme, Marta E.; Batuecas, Angel; Espinosa-Sanchez, Juan M.; Aran, Ismael; Lopez-Escamez, Jose A.

    2014-01-01

    Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10−8), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL. PMID:25397881

  2. Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.

    PubMed

    Cabrera, Sonia; Sanchez, Elena; Requena, Teresa; Martinez-Bueno, Manuel; Benitez, Jesus; Perez, Nicolas; Trinidad, Gabriel; Soto-Varela, Andrés; Santos-Perez, Sofía; Martin-Sanz, Eduardo; Fraile, Jesus; Perez, Paz; Alarcon-Riquelme, Marta E; Batuecas, Angel; Espinosa-Sanchez, Juan M; Aran, Ismael; Lopez-Escamez, Jose A

    2014-01-01

    Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.

  3. GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss.

    PubMed Central

    Iossa, Sandra; Marciano, Elio; Franzé, Annamaria

    2011-01-01

    The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermis and, in fact, GJB2 mutations have also been identified in syndromic disorders with hearing loss associated with various skin disease phenotypes. GJB2 mutations associated with skin disease are, in general, transmitted with a dominant inheritance pattern. Nonsyndromic deafness is caused prevalently by a loss-of-function, while literature evidences suggest for syndromic deafness a mechanism based on gain-of-function. The spectrum of skin manifestations associated with some mutations seems to have a very high phenotypic variability. Why some mutations can lead to widely varying cutaneous manifestations is poorly understood and in particular, the reason why the skin disease-deafness phenotypes differ from each other thus remains unclear. This review provides an overview of recent findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations with an emphasis on relevant clinical genotype-phenotype correlations. After describing connexin 26 fundamental characteristics, the most relevant and recent information about its known mutations involved in the syndromic forms causing hearing loss and skin problems are summarized. The possible effects of the mutations on channel expression and function are discussed. PMID:22547955

  4. GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss.

    PubMed

    Iossa, Sandra; Marciano, Elio; Franzé, Annamaria

    2011-11-01

    The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermis and, in fact, GJB2 mutations have also been identified in syndromic disorders with hearing loss associated with various skin disease phenotypes. GJB2 mutations associated with skin disease are, in general, transmitted with a dominant inheritance pattern. Nonsyndromic deafness is caused prevalently by a loss-of-function, while literature evidences suggest for syndromic deafness a mechanism based on gain-of-function. The spectrum of skin manifestations associated with some mutations seems to have a very high phenotypic variability. Why some mutations can lead to widely varying cutaneous manifestations is poorly understood and in particular, the reason why the skin disease-deafness phenotypes differ from each other thus remains unclear. This review provides an overview of recent findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations with an emphasis on relevant clinical genotype-phenotype correlations. After describing connexin 26 fundamental characteristics, the most relevant and recent information about its known mutations involved in the syndromic forms causing hearing loss and skin problems are summarized. The possible effects of the mutations on channel expression and function are discussed.

  5. Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss

    PubMed Central

    Bademci, G.; Cengiz, F. B.; Foster II, J.; Duman, D.; Sennaroglu, L.; Diaz-Horta, O.; Atik, T.; Kirazli, T.; Olgun, L.; Alper, H.; Menendez, I.; Loclar, I.; Sennaroglu, G.; Tokgoz-Yilmaz, S.; Guo, S.; Olgun, Y.; Mahdieh, N.; Bonyadi, M.; Bozan, N.; Ayral, A.; Ozkinay, F.; Yildirim-Baylan, M.; Blanton, S. H.; Tekin, M.

    2016-01-01

    The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies. PMID:27562378

  6. A deleterious mutation in the LOXHD1 gene causes autosomal recessive hearing loss in Ashkenazi Jews.

    PubMed

    Edvardson, S; Jalas, C; Shaag, A; Zenvirt, S; Landau, C; Lerer, I; Elpeleg, O

    2011-05-01

    Autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL) in Ashkenazi Jews, is mainly caused by mutations in the GJB2 and GJB6 genes. Here we describe a novel homozygous mutation of the LOXHD1 gene resulting in a premature stop codon (R1572X) in nine patients of Ashkenazi Jewish origin who had severe-profound congenital non-progressive ARNSHL and benefited from cochlear implants. Upon screening for the mutation among 719 anonymous Ashkenazi-Jews we detected four carriers, indicating a carrier rate of 1:180 Ashkenazi Jews. This is the second reported mutation in the LOXHD1 gene, and its homozygous presence in two of 39 Ashkenazi Jewish families with congenital ARNSHL suggest that it could account for some 5% of the familial cases in this community. Copyright © 2011 Wiley-Liss, Inc.

  7. Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss.

    PubMed

    Kasztelewicz, B; Czech-Kowalska, J; Lipka, B; Milewska-Bobula, B; Borszewska-Kornacka, M K; Romańska, J; Dzierżanowska-Fangrat, K

    2017-05-13

    Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

  8. A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment.

    PubMed

    Kytövuori, Laura; Hannula, Samuli; Mäki-Torkko, Elina; Sorri, Martti; Majamaa, Kari

    2017-09-28

    Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Application of SNPscan in Genetic Screening for Common Hearing Loss Genes

    PubMed Central

    Ke, Jia; Li, Tao; Hu, Ping; Song, Yu; Xu, Chiyu; Wang, Jie; Cheng, Jing; Zhang, Lei; Duan, Hong; Yuan, Huijun; Ma, Furong

    2016-01-01

    The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology. Genetic analysis of 115 variants in common genes related to HL, GJB2, SLC26A4 and MT-RNR, was performed on 695 subjects with non-syndromic hearing loss (NSHL) from the Northern China. The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MT-RNR1 variants. The variant allele frequency of GJB2, SLC26A4 and MT-RNR1 was 19.8% (275/1390), 21.9% (304/1390), and 0.86% (6/695), respectively. This approach can explain ~40% of NSHL cases and thus is a useful tool for establishing primary molecular diagnosis of NSHL in clinical genetics. PMID:27792752

  10. Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice.

    PubMed

    Chen, Mo; Wang, Qin; Zhu, Gang-Hua; Hu, Peng; Zhou, Yuan; Wang, Tian; Lai, Ruo-Sha; Xiao, Zi-An; Xie, Ding-Hua

    2016-10-28

    The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177-187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN(+/-) mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN(-/-) mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN(-/-) mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally-Mediated Gene Therapy

    PubMed Central

    Akil, Omar; Seal, Rebecca P.; Burke, Kevin; Wang, Chuansong; Alemi, Aurash; During, Matthew; Edwards, Robert H.; Lustig, Lawrence R.

    2012-01-01

    Summary Mice lacking the vesicular glutamate transporter-3 (VGLUT3) are congenitally deaf due to loss of glutamate release at the inner hair cell afferent synapse. Cochlear delivery of VGLUT3 using adeno-associated virus-1 (AAV1) leads to transgene expression in only inner hair cells (IHC), despite broader viral uptake. Within two weeks of AAV1-VGLUT3 delivery, acoustic brainstem response (ABR) thresholds normalize, along with partial rescue of the startle response. Lastly, we demonstrate partial reversal of the morphologic changes seen within the afferent IHC ribbon synapse. These findings represent the first successful restoration of hearing by gene replacement in mice, which is an important step towards gene therapy of human deafness. PMID:22841313

  12. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy.

    PubMed

    Akil, Omar; Seal, Rebecca P; Burke, Kevin; Wang, Chuansong; Alemi, Aurash; During, Matthew; Edwards, Robert H; Lustig, Lawrence R

    2012-07-26

    Mice lacking the vesicular glutamate transporter-3 (VGLUT3) are congenitally deaf due to loss of glutamate release at the inner hair cell afferent synapse. Cochlear delivery of VGLUT3 using adeno-associated virus type 1 (AAV1) leads to transgene expression in only inner hair cells (IHCs), despite broader viral uptake. Within 2 weeks of AAV1-VGLUT3 delivery, auditory brainstem response (ABR) thresholds normalize, along with partial rescue of the startle response. Lastly, we demonstrate partial reversal of the morphologic changes seen within the afferent IHC ribbon synapse. These findings represent a successful restoration of hearing by gene replacement in mice, which is a significant advance toward gene therapy of human deafness.

  13. A novel compound heterozygous mutation in the GJB2 gene causing non-syndromic hearing loss in a family.

    PubMed

    Wei, Qinjun; Liu, Youguo; Wang, Shuai; Liu, Tingting; Lu, Yajie; Xing, Guangqian; Cao, Xin

    2014-02-01

    Mutations in the GJB2 gene are responsible for up to 50% of cases of non-syndromic recessive hearing loss, with c.35delG, c.167delT and c.235delC being the predominant mutations in many world populations. However, a large number of rare mutations in this gene may also contribute to hearing loss. The aim of the present study was to conduct a clinical and molecular characterization of a Chinese family with non-syndromic hearing loss. Sequence analysis of the GJB2 gene led to the identification of a novel compound heterozygous mutation c.257C>G (p.T86R)/c.605ins46 in two profoundly deaf siblings whose hearing parents were each heterozygous, either for the c.257C>G (paternal) or for the c.605ins46 (maternal) mutations. Both c.257C>G and c.605ins46 are rare GJB2 mutations that have previously been reported to segregate with autosomal recessive hearing loss exclusively in East Asian populations. To study the pathogenic effect of the compound heterozygous mutation, a three-dimensional model was constructed and Anolea mean force potential energy was predicted for a bioinformatic structural analysis. HEK293 cells were used to study the pathogenic effect of mutant connexin 26 proteins. The results suggested that the c.257C>G (p.T86R)/c.605ins46 mutations in the GJB2 gene provides a novel molecular explanation for the role of the GJB2 gene in hearing loss.

  14. Mutation Analysis of the Common Deafness Genes in Patients with Nonsyndromic Hearing Loss in Linyi by SNPscan Assay.

    PubMed

    Zhang, Fengguo; Xiao, Yun; Xu, Lei; Zhang, Xue; Zhang, Guodong; Li, Jianfeng; Lv, Huaiqing; Bai, Xiaohui; Wang, Haibo

    2016-01-01

    Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss, GJB2, SLC26A4, and mtDNA12SrRNA are the major contributors. However, the mutation spectrum of these common deafness genes varies among different ethnic groups. The present work summarized mutations in these three genes and their prevalence in 339 patients with nonsyndromic hearing loss at three different special education schools and one children's hospital in Linyi, China. A new multiplex genetic screening system "SNPscan assay" was employed to detect a total of 115 mutations of the above three genes. Finally, 48.67% of the patients were identified with hereditary hearing loss caused by mutations in GJB2, SLC26A4, and mtDNA12SrRNA. The carrying rate of mutations in the three genes was 37.76%, 19.75%, and 4.72%, respectively. This mutation profile in our study is distinct from other parts of China, with high mutation rate of GJB2 suggesting a unique mutation spectrum in this area.

  15. Mutation Analysis of the Common Deafness Genes in Patients with Nonsyndromic Hearing Loss in Linyi by SNPscan Assay

    PubMed Central

    Zhang, Fengguo; Xu, Lei; Zhang, Xue; Zhang, Guodong; Li, Jianfeng; Lv, Huaiqing; Bai, Xiaohui; Wang, Haibo

    2016-01-01

    Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss, GJB2, SLC26A4, and mtDNA12SrRNA are the major contributors. However, the mutation spectrum of these common deafness genes varies among different ethnic groups. The present work summarized mutations in these three genes and their prevalence in 339 patients with nonsyndromic hearing loss at three different special education schools and one children's hospital in Linyi, China. A new multiplex genetic screening system “SNPscan assay” was employed to detect a total of 115 mutations of the above three genes. Finally, 48.67% of the patients were identified with hereditary hearing loss caused by mutations in GJB2, SLC26A4, and mtDNA12SrRNA. The carrying rate of mutations in the three genes was 37.76%, 19.75%, and 4.72%, respectively. This mutation profile in our study is distinct from other parts of China, with high mutation rate of GJB2 suggesting a unique mutation spectrum in this area. PMID:27247933

  16. A novel frameshift mutation of POU4F3 gene associated with autosomal dominant non-syndromic hearing loss

    SciTech Connect

    Lee, Hee Keun; Park, Hong-Joon; Lee, Kyu-Yup; Park, Rekil; Kim, Un-Kyung

    2010-06-04

    Autosomal dominant mutations in the transcription factor POU4F3 gene are associated with non-syndromic hearing loss in humans; however, there have been few reports of mutations in this gene worldwide. We performed a mutation analysis of the POU4F3 gene in 42 unrelated Koreans with autosomal dominant non-syndromic hearing loss, identifying a novel 14-bp deletion mutation in exon 2 (c.662del14) in one patient. Audiometric examination revealed severe bilateral sensorineural hearing loss in this patient. The novel mutation led to a truncated protein that lacked both functional POU domains. We further investigated the functional distinction between wild-type and mutant POU4F3 proteins using in vitro assays. The wild-type protein was completely localized in the nucleus, while the truncation of protein seriously affected its nuclear localization. In addition, the mutant failed to activate reporter gene expression. This is the first report of a POU4F3 mutation in Asia, and moreover our data suggest that further investigation will need to delineate ethnicity-specific genetic background for autosomal dominant non-syndromic hearing loss within Asian populations.

  17. Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

    PubMed

    Schraders, Margit; Ruiz-Palmero, Laura; Kalay, Ersan; Oostrik, Jaap; del Castillo, Francisco J; Sezgin, Orhan; Beynon, Andy J; Strom, Tim M; Pennings, Ronald J E; Zazo Seco, Celia; Oonk, Anne M M; Kunst, Henricus P M; Domínguez-Ruiz, María; García-Arumi, Ana M; del Campo, Miguel; Villamar, Manuela; Hoefsloot, Lies H; Moreno, Felipe; Admiraal, Ronald J C; del Castillo, Ignacio; Kremer, Hannie

    2012-11-02

    Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

  18. The association between GJB2 mutation and GJB6 gene in non syndromic hearing loss school children.

    PubMed

    Asma, A; Ashwaq, A; Norzana, A G; Atmadini, A Maizaton; Ruszymah, B H I; Saim, L; Wahida, I Farah

    2011-06-01

    Recently, molecular testing for GJB2 mutations has become the standard of care for the diagnosis of patients with non syndromic hearing impairment of unknown cause. The aims of this study are to determine the association between GJB2 mutation and GJB6 and to report the variation of mutations in deaf students who have heterozygous GJB2. This retrospective study was conducted at Universiti Kebangsaan Malaysia Medical Center (UKMMC). Data was collected from previous files and records from Tissue Engineering and Human Genetic Research Group Laboratory. Approval from Ethical Committee was obtained prior to the study. A total of 138 students have been screened in previous studies in UKMMC for the presence of GJB2 mutations as a cause for hearing loss. Thirty four of the 138 subjects have GJB2 mutations; 2 showed homozygous mutations whereas another 32 were heterozygous for GJB2 gene mutation. Only 31 DNA samples of students presented with sensorineural hearing loss with heterozygous mutation in GJB2 gene were included in this study. The sequencing results obtained were analyzed. The degree of hearing loss of those students with association between GJB2 mutation and GJB6 mutation will be discussed. Five out of 31 subjects (16.2%) have mutations in their GJB6 gene, suggesting a digenic inheritance of GJB2/GJB6 mutation. In total, four novel mutations were identified; E137D (n=1), R32Q (n=1), E101K (n=1) and Y156H (n=1) and one mutation deletion; 366delT (n=1). All students with association GJB2 mutation and GJB6 showed severe to profound hearing loss in both ears. Interestingly this study not detected the large deletion of 342 kb in GJB6 gene suggesting that the mutation is very rare in this region compared to certain parts of the world.

  19. Targeted Mutation of the Gene for Cellular Glutathione Peroxidase (Gpx1) Increases Noise-Induced Hearing Loss in Mice

    PubMed Central

    McFadden, Sandra L.; Ding, Da-Lian; Lear, Patricia M.; Ho, Ye-Shih

    2000-01-01

    Reactive oxygen species (ROS) and oxidative stress have been implicated in cochlear injury following loud noise and ototoxins. Genetic mutations that impair antioxidant defenses would be expected to increase cochlear injury following acute insults and to contribute to cumulative injury that presents as age-related hearing loss. We examined whether genetically based deficiency of cellular glutathione peroxidase, a major antioxidant enzyme, increases noise-induced hearing loss in mice. Two-month-old "knockout" mice with a targeted inactivating mutation of the gene coding for glutathione peroxidase (Gpx1) and wild type controls were exposed to broadband noise for one hour at 110 dB SPL. Auditory brainstem response (ABR) thresholds at test frequencies ranging from 5 to 40 kHz were obtained two and four weeks after exposure to determine the stable permanent component of the hearing loss. Depending on test frequency, Gpx1 knockout mice showed up to 16 dB higher ABR thresholds prior to noise exposure, and up to 15 dB greater noise-induced hearing loss, compared with controls. Within the cochlear base, there was also a significant contribution of the knockout to inner and outer hair cell loss, as well as nerve fiber loss. Our results support a link between genetic impairment of antioxidant defenses, vulnerability of the cochlea injury, and cochlear degeneration. Such impairment produces characteristics expected of some mutations associated with age-related hearing loss and offers one possible mechanism for their action. PMID:11545230

  20. A Novel De Novo Dominant Mutation in GJB2 Gene Associated with a Sporadic Case of Nonsyndromic Sensorineural Hearing Loss.

    PubMed

    Onsori, Habib; Rahmati, Mohammad; Fazli, Davood

    2014-12-01

    Mutations in the GJB2 gene are the most common known cause of hereditary congenital hearing loss. Rapid genomic DNA extraction (RGDE) method was used for genomic DNA extraction. After amplification of coding region of CX26 gene with specific primers, expected PCR products with 724bp length were subjected to direct sequencing in both directions. We describe here a novel heterozygous -T to -C transition at codon 202 (TGC→CGC) of the GJB2 gene in a patient, 40-year-old Iranian woman, which replaces a cysteine with an arginine residue (C202R). The dominant mutation C202R associated with non-syndromic sensorineural hearing loss. This mutation has not previously been described in affected or control samples from other populations investigated for GJB2 mutations, indicating that it is a rare substitution. This dominant mutation was recorded in NCBI GenBank with accession number KF 638275.

  1. A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine.

    PubMed

    Oh, Se-Kyung; Baek, Jeong-In; Weigand, Karl M; Venselaar, Hanka; Swarts, Herman G P; Park, Seong-Hyun; Hashim Raza, Muhammad; Jung, Da Jung; Choi, Soo-Young; Lee, Sang-Heun; Friedrich, Thomas; Vriend, Gert; Koenderink, Jan B; Kim, Un-Kyung; Lee, Kyu-Yup

    2015-05-01

    Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na(+)/K(+)-ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na(+)/K(+)-ATPase can be involved in both migraine and hearing loss.

  2. Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family.

    PubMed

    Ma, Yalin; Xiao, Yun; Zhang, Fengguo; Han, Yuechen; Li, Jianfeng; Xu, Lei; Bai, Xiaohui; Wang, Haibo

    2016-04-01

    Mutations in MYO7A gene have been reported to be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Most mutations in MYO7A gene caused USH1B, whereas only a few reported mutations led to DFNB2 and DFNA11. The current study was designed to investigate the mutations among a Chinese family with autosomal recessive hearing loss. In this study, we present the clinical, genetic and molecular characteristics of a Chinese family. Targeted capture of 127 known deafness genes and next-generation sequencing were employed to study the genetic causes of two siblings in the Chinese family. Sanger sequencing was employed to examine those variant mutations in the members of this family and other ethnicity-matched controls. We identified the novel compound heterozygous mutant alleles of MYO7A gene: a novel missense mutation c.3671C>A (p.A1224D) and a reported insert mutation c.390_391insC (p.P131PfsX9). Variants were further confirmed by Sanger sequencing. These two compound heterozygous variants were co-segregated with autosomal recessive hearing loss phenotype. The gene mutation analysis and protein sequence alignment further supported that the novel compound heterozygous mutations were pathogenic. The novel compound heterozygous mutations (c.3671C>A and c.390_391insC) in MYO7A gene identified in this study were responsible for the autosomal recessive sensorineural hearing loss of this Chinese family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Association between mutations in the gap junction β4 gene and nonsyndromic hearing loss: genotype-phenotype correlation patterns.

    PubMed

    Li, Tung-Cheng; Wang, Wen-Hung; Li, Chuan; Yang, Jiann-Jou

    2015-01-01

    Numerous studies have confirmed that gap junctions, composed of connexin (Cx) protein, are essential for auditory function. However, few studies have investigated the correlation between variants in the gap junction β4 (GJB4) gene and phenotype in patients with nonsyndromic hearing loss. Our previous study identified 11 patients with GJB4 gene variants in 253 unrelated patients with nonsyndromic hearing loss. In the present study, the phenotype-genotype correlation was examined in the 11 deaf patients with the different variants of GJB4. Analytical results revealed that the majority of probands had congenital hearing loss, which was bilateral, stable and without associated dermatological manifestations or morphological changes of the inner ear. An audiometric profile, including the observed consistency with severe-profound and flat shape dominance, may enable screening for variants of GJB4. On the basis of the above results, it was hypothesized that GJB4 may be a genetic risk factor for the development of nonsyndromic hearing loss and the data from the present study can be used to direct the clinical evaluation and effectively manage the care of families of children with GJB4.

  4. PSIP1/LEDGF: a new gene likely involved in sensorineural progressive hearing loss

    PubMed Central

    Girotto, Giorgia; Scheffer, Déborah I.; Morgan, Anna; Vozzi, Diego; Rubinato, Elisa; Di Stazio, Mariateresa; Muzzi, Enrico; Pensiero, Stefano; Giersch, Anne B.; Corey, David P.; Gasparini, Paolo

    2015-01-01

    Hereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554_1555del leading to p.E518Dfs*2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL. PMID:26689366

  5. Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis.

    PubMed

    Landry, Greg M; Hirata, Taku; Anderson, Jacob B; Cabrero, Pablo; Gallo, Christopher J R; Dow, Julian A T; Romero, Michael F

    2016-01-15

    Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization.

  6. Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis

    PubMed Central

    Landry, Greg M.; Hirata, Taku; Anderson, Jacob B.; Cabrero, Pablo; Gallo, Christopher J. R.; Dow, Julian A. T.

    2015-01-01

    Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization. PMID:26538444

  7. The DFNA2 locus for hearing impairment: two genes regulating K+ ion recycling in the inner ear.

    PubMed

    Van Hauwe, P; Coucke, P; Van Camp, G

    1999-10-01

    DFNA2 is a locus for autosomal dominant non-syndromal hearing impairment (ADNSHI) located on chromosome 1p34 and six linked families have been identified. An audiometric study of these families showed that despite small differences in the phenotype all families suffer from progressive hearing impairment starting in the high frequencies. A detailed genetic analysis revealed that this deafness locus contains more than one gene responsible for hearing impairment. Thus far, two genes on chromosome 1p34 have been implicated in ADNSHI. The first, connexin 31 (GJB3), is a member of the connexin gene family. Connexins form gap junctions. These are connections between neighbouring cells that allow transport of small molecules. GJB3 mutations were found in two small Chinese families with ADNSHI. The second is KCNQ4, a voltage-gated K+ channel. Mutations in KCNQ4 were first found in a small French family, later in five of the six linked DFNA2 families. No GJB3 or KCNQ4 mutations were detected in patients of an extended Indonesian DFNA2 family. Two pathways have been proposed for the recycling of K+ from the hair cells back to the endolymph. These pathways involve the use of gap junctions, K+ pumps and K+ channels. The expression of GJB3 and KCNQ4 in the inner ear and their functions suggest that both DFNA2 genes may play a role in K+ homeostasis.

  8. [Association between variations in protocadherin 15 gene and occupational noise-induced hearing loss].

    PubMed

    Xu, X R; Yang, Q Y; Jiao, J; Zheng, Y X; He, L H; Yu, S F; Gu, G Z; Chen, G S; Zhou, W H; Wu, H; Li, Y H; Zhang, H L; Zhang, Z R

    2017-01-06

    Objective: The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan(TM) Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. Results: The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M (P25, P75) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups (P=0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level or CNE

  9. Hearing Loss: Hearing Augmentation.

    PubMed

    Atcherson, Samuel R; Moreland, Christopher; Zazove, Philip; McKee, Michael M

    2015-07-01

    Etiologies of hearing loss vary. When hearing loss is diagnosed, referral to an otology subspecialist, audiology subspecialist, or hearing aid dispenser to discuss treatment options is appropriate. Conventional hearing aids provide increased sound pressure in the ear canal for detection of sounds that might otherwise be soft or inaudible. Hearing aids can be used for sensorineural, conductive, or mixed hearing loss by patients with a wide range of hearing loss severity. The most common type of hearing loss is high-frequency, which affects audibility and perception of speech consonants, but not vowels. As the severity of hearing loss increases, the benefit of hearing aids for speech perception decreases. Implantable devices such as cochlear implants, middle ear implants, and bone-anchored implants can benefit specific patient groups. Hearing assistive technology devices provide auditory, visual, or tactile information to augment hearing and increase environmental awareness of sounds. Hearing assistive devices include wireless assistive listening device systems, closed captioning, hearing aid-compatible telephones, and other devices. For some patients, financial barriers and health insurance issues limit acquisition of hearing aids, implantable devices, and hearing assistive devices. Physicians should be aware that for some patients and families, hearing augmentation may not be desired for cultural reasons.

  10. Two novel compound heterozygous families with a trimutation in the GJB2 gene causing sensorineural hearing loss.

    PubMed

    Martínez-Saucedo, Mirna; Mirna, Martínez-Saucedo; Rivera-Vega, María del Refugio; María Del Refugio, Rivera-Vega; Gonzalez--Huerta Luz, María; María, Gonzalez-Huerta Luz; Urueta-Cuellar, Héctor; Héctor, Urueta-Cuellar; Toral-López, Jaime; Jaime, Toral-López; Berruecos-Villalobos, Pedro; Pedro, Berruecos-Villalobos; Cuevas-Covarrubias, Sergio; Sergio, Cuevas-Covarrubias

    2015-12-01

    Sensorineural hearing loss (SNHL) is a genetically heterogeneous disease. GJB2 gene mutations seem to be the most frequent cause of hereditary hearing impairment in several populations. There is variability in the mutations in the GJB2 gene worldwide; this remarks the influence of ethnic background in SNHL. To describe the presence of two trimutations in the GJB2 gene in two Mexican families with hereditary SNHL. Two unrelated Mexican families with prelingual SNHL were included in the study. Analysis of the GJB2 gene through PCR and DNA direct sequencing analysis was performed in all members of the families and in 100 normal controls. Affected member of the family 1 showed the trimutation p.S19R/p.R32S/p.E47*, whereas affected members of the family 2 showed the trimutation p.F31I/p.W44*/p.V84M. Parents of both families were heterozygous with normal audition. We found a novel mutation in the GJB2 gene and two trimutations with SNHL not previously reported. This remarks the complexity in the pattern of mutations in the GJB2 gene in SNHL and enriches the spectrum of the type of molecular defects in the GJB2 gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss.

    PubMed

    Dahmani, Malika; Ammar-Khodja, Fatima; Bonnet, Crystel; Lefèvre, Gaelle M; Hardelin, Jean-Pierre; Ibrahim, Hassina; Mallek, Zahia; Petit, Christine

    2015-08-19

    More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss. After exclusion of GJB2 (the gene most frequently involved in non-syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling. A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in EPS8L2, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells' stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database. Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode.

  12. Update of the spectrum of GJB2 gene mutations in 152 Moroccan families with autosomal recessive nonsyndromic hearing loss.

    PubMed

    Bakhchane, Amina; Bousfiha, Amale; Charoute, Hicham; Salime, Sara; Detsouli, Mustapha; Snoussi, Khalid; Nadifi, Sellama; Kabine, Mostafa; Rouba, Hassan; Dehbi, Hind; Roky, Rachida; Charif, Majida; Barakat, Abdelhamid

    2016-06-01

    Deafness is one of the most common genetic diseases in humans and is subject to important genetic heterogeneity. The most common cause of non syndromic hearing loss (NSHL) is mutations in the GJB2 gene. This study aims to update and evaluate the spectrum of GJB2 allele variants in 152 Moroccan multiplex families with non syndromic hearing loss. Seven different mutations were detected: c.35delG, p.V37I, p.E47X, p.G200R, p.Del120E, p.R75Q, the last three mutations were described for the first time in Moroccan deaf patients, in addition to a novel nonsense mutation, the c.385G>T which is not referenced in any database. Sixty six families (43.42%) have mutations in the coding region of GJB2, while the homozygous c.35delG mutation still to date the most represented 51/152 (33.55%). The analysis of the geographical distribution of mutations located in GJB2 gene showed more allelic heterogeneity in the north and center compared to the south of Morocco. Our results showed that the GJB2 gene is a major contributor to non syndromic hearing loss in Morocco. Thus, this report of the GJB2 mutations spectrum all over Morocco has an important implication for establishing a suitable molecular diagnosis.

  13. Targeted Gene Capture and Massively Parallel Sequencing Identify TMC1 as the Causative Gene in a Six-generation Chinese Family with Autosomal Dominant Hearing Loss

    PubMed Central

    Gao, Xue; Huang, Sha-Sha; Yuan, Yong-Yi; Wang, Guo-Jian; Xu, Jin-Cao; Ji, Yu-Bin; Han, Ming-Yu; Yu, Fei; Kang, Dong-Yang; Lin, Xi; Dai, Pu

    2015-01-01

    Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the transmembrane channel-like gene1 (TMC1) are known to cause autosomal dominant and recessive forms of nonsyndromic hearing loss linked to the loci of DFNA36 and DFNB7/11, respectively. We characterized a six-generation Chinese family (5315) with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 82 known deafness genes, next-generation sequencing and bioinformatic analysis, we identified TMC1 c.1714G>A (p. D572N) as the disease-causing mutation. This mutation co-segregated with hearing loss in other family members and was not detected in 308 normal controls. In order to determine the prevalence of TMC1 c.1714G>A in Chinese ADNSHL families, we used DNA samples from 67 ADNSHL families with sloping audiogram and identified two families carry this mutation. To determine whether it arose from a common ancestor, we analyzed nine STR markers. Our results indicated that TMC1 c.1714G>A (p.D572N) account for about 4.4% (3/68) of ADNSHL in the Chinese population. PMID:26079994

  14. Pan-Canadian REspiratory STandards INitiative for Electronic Health Records (PRESTINE): 2011 National Forum Proceedings

    PubMed Central

    Lougheed, M Diane; Minard, Janice; Dworkin, Shari; Juurlink, Mary-Ann; Temple, Walley J; To, Teresa; Koehn, Marc; Van Dam, Anne; Boulet, Louis-Philippe

    2012-01-01

    stakeholders across the spectrum of respiratory care, including clinicians, researchers, health informaticists and administrators to explore and recommend a potential scope, approach and governance structure for this important project. The Pan-Canadian REspiratory STandards INitiative for Electronic Health Records (PRESTINE) goal is to recommend respiratory data elements and standards for use in electronic medical records across Canada that meet the needs of providers, administrators, researchers and policy makers to facilitate evidence-based clinical care, monitoring, surveillance, benchmarking and policy development. The focus initially is expected to include asthma, chronic obstructive pulmonary disease and pulmonary function standards elements that are applicable to many respiratory conditions. The present article summarizes the process and findings of the forum deliberations. PMID:22536581

  15. Pan-Canadian REspiratory STandards INitiative for Electronic Health Records (PRESTINE): 2011 national forum proceedings.

    PubMed

    Lougheed, M Diane; Minard, Janice; Dworkin, Shari; Juurlink, Mary-Ann; Temple, Walley J; To, Teresa; Koehn, Marc; Van Dam, Anne; Boulet, Louis-Philippe

    2012-01-01

    stakeholders across the spectrum of respiratory care, including clinicians, researchers, health informaticists and administrators to explore and recommend a potential scope, approach and governance structure for this important project. The Pan-Canadian REspiratory STandards INitiative for Electronic Health Records (PRESTINE) goal is to recommend respiratory data elements and standards for use in electronic medical records across Canada that meet the needs of providers, administrators, researchers and policy makers to facilitate evidence-based clinical care, monitoring, surveillance, benchmarking and policy development. The focus initially is expected to include asthma, chronic obstructive pulmonary disease and pulmonary function standards elements that are applicable to many respiratory conditions. The present article summarizes the process and findings of the forum deliberations.

  16. Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss.

    PubMed

    Lesperance, Marci M; Hall, James W; San Agustin, Theresa B; Leal, Suzanne M

    2003-04-01

    To describe low-frequency sensorineural hearing loss (LFSNHL) inherited as a dominant trait in 3 families and in 1 sporadic case. Longitudinal clinical study from 1968 to 2001. Tertiary care hospital; field studies conducted by molecular genetic research laboratory. Dominant LFSNHL families. Questionnaires, serial audiograms, and interviews, correlated with molecular genetic data. Symptoms, age of onset, serial audiometric data, and hearing aid use. Low-frequency sensorineural hearing loss is typically diagnosed in the first decade and slowly progresses over decades; LFSNHL is often asymptomatic in young patients, few of whom use hearing aids. Speech perception becomes affected in later decades when patients develop high-frequency loss. Even children with a strong family history of dominant LFSNHL were not monitored routinely. Penetrance appears complete in that all individuals with a genetic mutation developed hearing loss. Dominant LFSNHL is most commonly caused by mutations in the Wolfram syndrome type 1 gene (WFS1). Mutations in WFS1 also cause a rare recessive syndromic form of hearing loss known as Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Routine newborn hearing screening methods will not typically identify hearing loss affecting frequencies below 2000 Hz; thus, children at risk must be specifically monitored. Genetic counseling and genetic testing may be useful in the management of patients with this type of hearing loss.

  17. Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

    PubMed

    György, Bence; Sage, Cyrille; Indzhykulian, Artur A; Scheffer, Deborah I; Brisson, Alain R; Tan, Sisareuth; Wu, Xudong; Volak, Adrienn; Mu, Dakai; Tamvakologos, Panos I; Li, Yaqiao; Fitzpatrick, Zachary; Ericsson, Maria; Breakefield, Xandra O; Corey, David P; Maguire, Casey A

    2017-02-01

    Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. Exo-AAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo. Exo-AAV shows no toxicity in vivo, as assayed by tests of auditory and vestibular function. Finally, exo-AAV1 gene therapy partially rescues hearing in a mouse model of hereditary deafness (lipoma HMGIC fusion partner-like 5/tetraspan membrane protein of hair cell stereocilia [Lhfpl5/Tmhs(-/-)]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.

  18. A novel mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with non-syndromic sensorineural hearing impairment.

    PubMed

    Hutchin, T P; Parker, M J; Young, I D; Davis, A C; Pulleyn, L J; Deeble, J; Lench, N J; Markham, A F; Mueller, R F

    2000-09-01

    We describe a family with non-syndromic sensorineural hearing impairment inherited in a manner consistent with maternal transmission. Affected members were found to have a novel heteroplasmic mtDNA mutation, T7510C, in the tRNA(Ser(UCN)) gene. This mutation was not found in 661 controls, is well conserved between species, and disrupts base pairing in the acceptor stem of the tRNA, making it the probable cause of hearing impairment in this family. Sequencing of the other mitochondrial tRNA genes did not show any other pathogenic mutations. Four other mutations causing hearing impairment have been reported in the tRNA(Ser(UCN)) gene, two having been shown to affect tRNA(Ser(UCN)) levels. With increasing numbers of reports of mtDNA mutations causing hearing impairment, screening for such mutations should be considered in all cases unless mitochondrial inheritance can be excluded for certain.

  19. Autosomal dominant hearing loss resulting from p.R75Q mutation in the GJB2 gene: nonsyndromic presentation in a South Indian family.

    PubMed

    Pavithra, Amritkumar; Selvakumari, Mathiyalagan; Nityaa, Venkatesan; Sharanya, Narasimhan; Ramakrishnan, Rajagopalan; Narasimhan, Murali; Srisailapathy, C R Srikumari

    2015-01-01

    Mutations in the GJB2 gene encoding the gap junction protein Connexin 26 have been associated with autosomal recessive as well as dominant nonsyndromic hearing loss. Owing to the involvement of connexins in skin homeostasis, GJB2 mutations have also been associated with syndromic forms of hearing loss showing various skin manifestations. We report an assortatively mating hearing impaired family of south Indian origin with three affected members spread over two generations, having p.R75Q mutation in the GJB2 gene in the heterozygous condition. The inheritance pattern was autosomal dominant with mother and son being affected. Dermatological and histopathologic examinations showed absence of palmoplantar keratoderma. To the best of our knowledge, this is the first report from India on p.R75Q mutation in the GJB2 gene with nonsyndromic hearing loss.

  20. Impact of methionine synthase gene and methylenetetrahydrofolate reductase gene polymorphisms on the risk of sudden sensorineural hearing loss.

    PubMed

    Gross, Menachem; Friedman, Gideon; Eliashar, Ron; Koren-Morag, Nira; Goldschmidt, Neta; Atta, Iman Abou; Ben-Yehuda, Arie

    2006-01-01

    Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG--7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG--3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL.

  1. Mutations in Cockayne Syndrome-Associated Genes (Csa and Csb) Predispose to Cisplatin-Induced Hearing Loss in Mice

    PubMed Central

    Rainey, Robert N.; Ng, Sum-yan; Llamas, Juan; van der Horst, Gijsbertus T. J.

    2016-01-01

    sensorineural hearing loss. We show that mouse models of Cockayne syndrome, a progeroid disorder resulting from a defect in the transcription-coupled DNA repair (TCR) branch of nucleotide excision repair, are hypersensitive to cisplatin-induced hearing loss and sensory hair cell death in the organ of Corti, the mammalian auditory sensory epithelium. Our work indicates that Csa and Csb, two genes involved in TCR, are preferentially required to protect against cisplatin ototoxicity, relative to global genome repair-specific elements of nucleotide excision repair, and suggests that TCR is a major force maintaining DNA integrity in the cochlea. The Cockayne syndrome mice thus represent a model for testing the contribution of DNA repair mechanisms to cisplatin ototoxicity. PMID:27122034

  2. Identification of a novel mutation in the SLC26A4 gene in an Italian with fluctuating sensorineural hearing loss.

    PubMed

    Cama, Elona; Alemanno, Maria Stella; Bellacchio, Emanuele; Santarelli, Rosamaria; Carella, Massimo; Zelante, Leopoldo; Palladino, Teresa; Inches, Ingrid; di Paola, Francesco; Arslan, Edoardo; Melchionda, Salvatore

    2009-10-01

    Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goitre and defective iodide organification. Congenital and profound hearing loss is the hallmark of the syndrome, while goitre and thyroid dysfunction are highly variable even within the same family. Clinical features are due to altered formation of pendrin, a chloride/iodide transporter protein expressed in the inner ear, thyroid gland and kidney. A novel substitution was found in exon 7 of the pendrin encoding gene (SLC26A4) that leads to a stop codon, S314X. The new variation was found in compound heterozygosity with L445W mutation in a hearing impaired patient with bilateral Mondini's dysplasia and goitre.

  3. Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model.

    PubMed

    Zheng, Lili; Zheng, Jing; Whitlon, Donna S; García-Añoveros, Jaime; Bartles, James R

    2010-05-26

    We have developed an advantageous epithelial cell transfection model for examining the targeting, interactions, and mutations of hair cell proteins. When expressed in LLC-PK1-CL4 epithelial cells (CL4 cells), the outer hair cell protein prestin showed faithful domain-specific targeting to the basolateral plasma membrane. We examined the consequences of mutations affecting prestin activity and assigned a targeting role to the cytoplasmic tail. The stereociliary link protein cadherin 23 (Cdh23) was targeted to the plasma membrane of CL4 cell microvilli, the topological equivalent of stereocilia. In cells coexpressing the Cdh23 cytoplasmic binding protein harmonin, a large fraction of harmonin became colocalized with Cdh23 in microvilli. Using this assay and in vitro protein binding assays, we formulated an alternative model for Cdh23-harmonin binding, in which the primary interaction is between the harmonin N-domain and a 35-residue internal peptide in the Cdh23 cytoplasmic tail. Contrary to a previous model, we found no role for the Cdh23 C-terminal PDZ (PSD-95/Dlg/ZO-1)-binding motif and observed that Cdh23 bound similar levels of harmonin with or without the exon 68 peptide. We also examined two proteins involved in stereocilium elongation. The stereociliary actin-bundling protein espin was targeted to CL4 cell microvilli and caused microvillar elongation, whereas espin with the c.2469delGTCA or c.1988delAGAG human deafness mutation showed defects in microvillar targeting and elongation. The unconventional myosin motor myosin XVa accumulated at the tips of espin-elongated microvilli, by analogy to its location in stereocilia, whereas myosin XVa with the c.4351G>A or c.4669A>G human deafness mutation did not, revealing functional deficits in motor activity.

  4. Hereditary Hearing Loss.

    ERIC Educational Resources Information Center

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  5. Hereditary Hearing Loss.

    ERIC Educational Resources Information Center

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  6. Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss.

    PubMed

    Riahi, Zied; Hammami, Hassen; Ouragini, Houyem; Messai, Habib; Zainine, Rim; Bouyacoub, Yosra; Romdhane, Lilia; Essaid, Donia; Kefi, Rym; Rhimi, Mohsen; Bedoui, Monia; Dhaouadi, Afef; Feldmann, Delphine; Jonard, Laurence; Besbes, Ghazi; Abdelhak, Sonia

    2013-08-01

    Hearing loss is the most frequent sensory disorder. It affects 3 in 1000 newborns. It is genetically heterogeneous with 60 causally-related genes identified to date. Mutations in GJB2 gene account for half of all cases of non-syndromic deafness. The aim of this study was to determine the relative frequency of GJB2 allele variants in Tunisia. In this study, we screened 138 patients with congenital hearing loss belonging to 131 families originating from different parts of Tunisia for mutations in GJB2 gene. GJB2 mutations were found in 39% of families (51/131). The most common mutation was c.35delG accounting for 35% of all cases (46/131). The second most frequent mutation was p.E47X present in 3.8% of families. Four identified mutations in our cohort have not been reported in Tunisia; p.V37I, c.235delC, p.G130A and the splice site mutation IVS1+1G>A (0.76%). These previously described mutations were detected only in families originating from Northern and not from other geographical regions in Tunisia. In conclusion we have confirmed the high frequency of c.35delG in Tunisia which represents 85.4% of all GJB2 mutant alleles. We have also extended the mutational spectrum of GJB2 gene in Tunisia and revealed a more pronounced allelic heterogeneity in the North compared to the rest of the country.

  7. [Association between single nucleotide polymorphismsin human heat shock protein 70 gene and susceptibility to noise-induced hearing loss].

    PubMed

    Li, Y H; Chen, G S; Jiao, J; Zhou, W H; Wu, H; Gu, G Z; Zhang, H L; Zheng, Y X; Yu, S F

    2016-12-20

    Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) at rs1043618, rs2075800, and rs2763979 in human heat shock protein 70 (HSP70) gene and susceptibility to noise-induced hearing loss (NIHL) . Methods: A case-control study was performed, and 5 934 workers exposed to noise in an iron and steel plant in Henan, China, who underwent physical examination from 2006 to 2015, were enrolled as study subjects. According to the criteria of binaural average high - frequency (3000, 4000, and 6000 Hz) hearing threshold≥40 dB (HL) and monauralaverage speech-frequency (500, 1000, 2000 Hz) hearing threshold≥26 dB (HL) on the basis of binauralhigh frequency loss measured by pure tone audiometry, as well as the exclusion of NIHL, a total of 286 workers were enrolled as hearing loss group; after the adjustment for sex, type of work, age (difference≤5 years) , and working years of noise exposure (difference ≤2 years) , 286 workers were enrolled as control group. A 2 ml blood genomic DNA extraction kit was used to perform DNA extraction for the peripheral blood samples, and a multiple SNP typing kit was used to determine the genotypes at the three loci in 572 samples. The association between the SNPs at the three loci and susceptibility to NIHL was analyzed. Results: In all workers, the equivalent sound level (L(Aeq)) of noise was 75.0~96.8 dB (A) . The hearing loss group had a significantly higher binauralhigh - frequencyhearing threshold than the control group (t=56.908, P<0.05) . With CC+TC genotype as control, TT genotype at rs2763979 in HSP70 gene was associated with the susceptibility to NIHL (OR=1.731, 95%CI 1.021-2.935) . In the group with cumulative noise exposure of 96 dB (A) ·year, TT genotype at rs2763979was associated with the susceptibility to NIHL (OR=5.694, 95%CI 1.256-25.817) . The rs1043618 and rs2075800 loci of HSP70 were not associated with the susceptibility to NIHL (both P>0.05) . After the adjustment for

  8. The Study of SLC26A4 Gene Causing Autosomal Recessive Hearing Loss by Linkage Analysis in a Cohort of Iranian Populations

    PubMed Central

    Reiisi, Somayeh; Sanati, Mohammad Hosein; Tabatabaiefar, Mohammad Amin; Ahmadian, Shahla; Reiisi, Salimeh; Parchami, Shahrbanoo; Porjafari, Hamid; Shahi, Heshmat; Shavarzi, Afsaneh; Hashemzade Chaleshtori, Morteza

    2014-01-01

    Sensorineural non-syndromic hearing loss is the most common disorder which affects 1 in 500 newborns. Hearing loss is an extremely heterogeneous defect with more than 100 loci identified to date. According to the studies, mutations in GJB2 are estimated to be involved in 50- 80% of autosomal recessive non-syndromic hearing loss cases, but contribution of other loci in this disorder is yet ambiguous. With regard to studies, DFNB4 locus (SLC26A4) can be classified as the second cause of hearing loss. So, this study aimed to determine the contribution of this locus in hearing loss as well as the frequency of SLC26A4 gene mutations in a population in the west of Iran. In this descriptive laboratory study, we included 30 families from the west of Iran with no mutation in GJB2 gene. Linkage analysis was performed by DFNB4 (SLC26A4) molecular markers (STR). The families with hearing loss linked to this locus were further analyzed for mutation detection. SLC26A4 gene exons were amplified and analyzed using direct DNA sequencing. In studied families, 2 families displayed linkage to DFNB4 locus. Identified mutations include mutation in exon 5 (c.416 G>T) and in splicing site of exon 7 (IVS-2 A>G or c.919-2 A>G). PMID:25317404

  9. Age-related hearing loss

    MedlinePlus

    ... grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following factors contribute to age-related hearing loss: Family history (age-related hearing loss tends to run in ...

  10. The Genetic Architecture of Noise-Induced Hearing Loss: Evidence for a Gene-by-Environment Interaction

    PubMed Central

    Lavinsky, Joel; Ge, Marshall; Crow, Amanda L.; Pan, Calvin; Wang, Juemei; Salehi, Pezhman; Myint, Anthony; Eskin, Eleazar; Allayee, Hooman; Lusis, Aldons J.; Friedman, Rick A.

    2016-01-01

    The discovery of environmentally specific genetic effects is crucial to the understanding of complex traits, such as susceptibility to noise-induced hearing loss (NIHL). We describe the first genome-wide association study (GWAS) for NIHL in a large and well-characterized population of inbred mouse strains, known as the Hybrid Mouse Diversity Panel (HMDP). We recorded auditory brainstem response (ABR) thresholds both pre and post 2-hr exposure to 10-kHz octave band noise at 108 dB sound pressure level in 5–6-wk-old female mice from the HMDP (4–5 mice/strain). From the observation that NIHL susceptibility varied among the strains, we performed a GWAS with correction for population structure and mapped a locus on chromosome 6 that was statistically significantly associated with two adjacent frequencies. We then used a “genetical genomics” approach that included the analysis of cochlear eQTLs to identify candidate genes within the GWAS QTL. In order to validate the gene-by-environment interaction, we compared the effects of the postnoise exposure locus with that from the same unexposed strains. The most significant SNP at chromosome 6 (rs37517079) was associated with noise susceptibility, but was not significant at the same frequencies in our unexposed study. These findings demonstrate that the genetic architecture of NIHL is distinct from that of unexposed hearing levels and provide strong evidence for gene-by-environment interactions in NIHL. PMID:27520957

  11. Single Nucleotide Polymorphisms of the GJB2 and GJB6 Genes Are Associated with Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Grillo, Ana Paula; de Oliveira, Flávia Marcorin; de Carvalho, Gabriela Queila; Medrano, Ruan Felipe Vieira; da Silva-Costa, Sueli Matilde; Sartorato, Edi Lúcia; de Oliveira, Camila Andréa

    2015-01-01

    Single nucleotide polymorphisms (SNPs) are important markers in many studies that link DNA sequence variations to phenotypic changes; such studies are expected to advance the understanding of human physiology and elucidate the molecular basis of diseases. The DFNB1 locus, which contains the GJB2 and GJB6 genes, plays a key role in nonsyndromic hearing loss. Previous studies have identified important mutations in this locus, but the contribution of SNPs in the genes has not yet been much investigated. The aim of this study was to investigate the association of nine polymorphisms located within the DFNB1 locus with the occurrence of autosomal recessive nonsyndromic hearing loss (ARNSHL). The SNPs rs3751385 (C/T), rs7994748 (C/T), rs7329857 (C/T), rs7987302 (G/A), rs7322538 (G/A), rs9315400 (C/T), rs877098 (C/T), rs945369 (A/C), and rs7333214 (T/G) were genotyped in 122 deaf patients and 132 healthy controls using allele-specific PCR. There were statistically significant differences between patients and controls, in terms of allelic frequencies in the SNPs rs3751385, rs7994748, rs7329857, rs7987302, rs945369, and rs7333214 (P < 0.05). No significant differences between the two groups were observed for rs7322538, rs9315400, and rs877098. Our results suggest that SNPs present in the GJB2 and GJB6 genes may have an influence on ARNSHL in humans. PMID:26075227

  12. Autosomal dominant prelingual hearing loss with palmoplantar keratoderma syndrome: Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene.

    PubMed

    Birkenhäger, Ralf; Lüblinghoff, Nicola; Prera, Erick; Schild, Christian; Aschendorff, Antje; Arndt, Susan

    2010-07-01

    About one to three of a 1,000 neonates are afflicted at birth with a serious hearing impairment, with about half of the cases due to genetic causes. Genetic causes of hearing impairment are very heterogeneous. About half of all cases of genetically caused nonsyndromic hearing loss can be ascribed to mutations in the GJB2 gene (connexin 26) and to deletions in the GJB6 gene(connexin 30). Thus far, about 90 different mutations have been identified in the GJB2 gene, of which the majority are autosomal recessive. Ten mutations are autosomal dominant and are in most cases associated with various skin diseases: the keratitis-ichthyosis-deafness (KID) syndrome, Vohwinkel syndrome and palmoplantar keratoderma with deafness. To date, the following mutations have been identified which lead to the Palmoplantar Keratoderma syndrome with deafness; Gly59Ala, Gly59Arg, His73Arg, Arg75Trp, and Arg75Gln. We are reporting on four patients with severe hearing impairment. They are members of three unrelated families, who are carriers of mutations Arg75Trp or Arg75Gln, but unlike patients of other publications, do not all present with Palmoplantar Keratoderma syndrome. Our investigations document additional evidence for the correlation between the cited mutations in the GJB2 gene and a syndromic hearing impairment with palmoplantar keratoderma.

  13. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations.

    PubMed

    Albert, Sébastien; Blons, Hélène; Jonard, Laurence; Feldmann, Delphine; Chauvin, Pierre; Loundon, Nathalie; Sergent-Allaoui, Annie; Houang, Muriel; Joannard, Alain; Schmerber, Sébastien; Delobel, Bruno; Leman, Jacques; Journel, Hubert; Catros, Hélène; Dollfus, Hélène; Eliot, Marie-Madeleine; David, Albert; Calais, Catherine; Drouin-Garraud, Valérie; Obstoy, Marie-Françoise; Tran Ba Huy, Patrice; Lacombe, Didier; Duriez, Françoise; Francannet, Christine; Bitoun, Pierre; Petit, Christine; Garabédian, Eréa-Noël; Couderc, Rémy; Marlin, Sandrine; Denoyelle, Françoise

    2006-06-01

    Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.

  14. [Research on mitochondrial DNA T1095C gene variation in military noise-induced hearing loss].

    PubMed

    Qu, Li; Xue, Xijun; Dai, Pu; Han, Dongyi; Cao, Xianbao; Yang, Xiaodong; Shao, Fuyin; Zhang, Bo; Ma, Tao; Yu, Ruili; Zhong, Ling

    2010-05-01

    To study the clinical and sequence character of the entire mitochondrial genome in five subjects with mitochondrial 12SrRNA T1095C mutation, and to analyze its relationship with the military noise-induced hearing loss (NIHL). Three hundreds and four soldiers exposed to military noise were selected in Yunan and Beijing, including susceptible (experimental) and tolerance (control) groups. Mitochondrial 12SrRNA T1095C mutation were found in 5 subjects. Then the complete nucleotide sequence of five subjects were sequenced and its clinical character were analyzed. m12SrRNA T1095C mutation were identified in 5 subjects of experimental group,and none were found in control group. There was significant difference between them (P < 0.05). All five soldiers had the history of military noise exposure and showed sensorineural deafness of different degrees. Sequence analysis of the complete mitochondrial genomes showed the distinct sets of mtDNA polymorphism besides T1095C mutation in five subjects. The T1095C mutation in hearing loss subjects with various genetic background and history of military noise exposure, is involved in the pathogenesis of hearing impairment. It indicates that the T1095C mutation do relate well with military noise induced-hearing loss.

  15. A Missense Mutation in the Mouse Col2a1 Gene Causes Spondyloepiphyseal Dysplasia Congenita, Hearing Loss, and Retinoschisis

    PubMed Central

    DONAHUE, LEAH RAE; CHANG, BO; MOHAN, SUBBURAMAN; MIYAKOSHI, NAO; WERGEDAL, JON E; BAYLINK, DAVID J; HAWES, NORMAN L; ROSEN, CLIFFORD J; WARD-BAILEY, PATRICIA; ZHENG, QING Y; BRONSON, RODERICK T; JOHNSON, KENNETH R; DAVISSON, MURIEL T

    2010-01-01

    A missense mutation in the mouse Col2a1 gene has been discovered, resulting in a mouse phenotype with similarities to human spondyloepiphyseal dysplasia (SED) congenita. In addition, SED patients have been identified with a similar molecular mutation in human COL2A1. This mouse model offers a useful tool for molecular and biological studies of bone development and pathology. Introduction A new mouse autosomal recessive mutation has been discovered and named spondyloepiphyseal dysplasia congenita (gene symbol sedc). Materials and Methods Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora, and tibias, plus retinoschisis and hearing loss. The mutation was mapped to Chr15, and Col2a1 was identified as a candidate gene. Results Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417. Two human patients with spondyloepiphyseal dysplasia (SED) congenita have been reported with the same amino acid substitution at position 789 in the human COL2A1 gene. Conclusions Thus, sedc/sedc mice provide a valuable model of human SED congenita with molecular and phenotypic homology. Further biochemical analyses, molecular modeling, and cell culture studies using sedc/sedc mice could provide insight into mechanisms of skeletal development dependent on Col2a1 and its role in fibril formation and cartilage template organization. PMID:12968670

  16. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients.

    PubMed

    Mori, Kentaro; Moteki, Hideaki; Miyagawa, Maiko; Nishio, Shin-Ya; Usami, Shin-Ichi

    2016-01-01

    Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500-1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434) and the total numbers of cases associated with at least one mutation was 44.07% (316/717). Among these, we were able to diagnose 212 (30%) patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8%) had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall) were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes.

  17. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients

    PubMed Central

    Mori, Kentaro; Moteki, Hideaki; Miyagawa, Maiko; Nishio, Shin-ya; Usami, Shin-ichi

    2016-01-01

    Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500–1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434) and the total numbers of cases associated with at least one mutation was 44.07% (316/717). Among these, we were able to diagnose 212 (30%) patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8%) had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall) were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes. PMID:27627659

  18. New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian patients with non-syndromic hearing loss

    SciTech Connect

    Mkaouar-Rebai, Emna Tlili, Abdelaziz; Masmoudi, Saber; Charfeddine, Ilhem; Fakhfakh, Faiza

    2008-05-09

    The 12S rRNA gene was shown to be a hot spot for aminoglycoside-induced and non-syndromic hearing loss since several deafness-associated mtDNA mutations were identified in this gene. Among them, we distinguished the A1555G, the C1494T and the T1095C mutations and C-insertion or deletion at position 961. One hundred Tunisian patients with non-syndromic hearing loss and 100 hearing individuals were analysed in this study. A PCR-RFLP analysis with HaeIII restriction enzyme showed the presence of the A1555G mutation in the 12S rRNA gene in only one out of the 100 patients. In addition, PCR-RFLP and radioactive PCR revealed the presence of a new HaeIII polymorphic restriction site in the same gene of 12S rRNA site in 4 patients with non-syndromic hearing loss. UVIDOC-008-XD analyses showed the presence of this new polymorphic restriction site with a variable heteroplasmic rates at position +1517 of the human mitochondrial genome. On the other hand, direct sequencing of the entire mitochondrial 12S rRNA gene in the 100 patients and in 100 hearing individuals revealed the presence of the A750G and A1438G polymorphisms and the absence of the C1494T, T1095C and 961insC mutations in all the tested individuals. Sequencing of the whole mitochondrial genome in the 4 patients showing the new HaeIII polymorphic restriction site revealed only the presence of the A8860G transition in the MT-ATP6 gene and the A4769G polymorphism in the ND2 gene.

  19. A Point Mutation in the Gene for Asparagine-Linked Glycosylation 10B (Alg10b) Causes Nonsyndromic Hearing Impairment in Mice (Mus musculus)

    PubMed Central

    Probst, Frank J.; Corrigan, Rebecca R.; del Gaudio, Daniela; Salinger, Andrew P.; Lorenzo, Isabel; Gao, Simon S.; Chiu, Ilene; Xia, Anping

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway. PMID:24303013

  20. A point mutation in the gene for asparagine-linked glycosylation 10B (Alg10b) causes nonsyndromic hearing impairment in mice (Mus musculus).

    PubMed

    Probst, Frank J; Corrigan, Rebecca R; Del Gaudio, Daniela; Salinger, Andrew P; Lorenzo, Isabel; Gao, Simon S; Chiu, Ilene; Xia, Anping; Oghalai, John S; Justice, Monica J

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

  1. Investigation of LRTOMT gene (locus DFNB63) mutations in Iranian patients with autosomal recessive non-syndromic hearing loss

    PubMed Central

    Taghizadeh, Seyyed Hossein; Kazeminezhad, Seyyed Reza; Sefidgar, Seyyed Ali Asghar; Yazdanpanahi, Nasrin; Tabatabaeifar, Mohammad Amin; Yousefi, Ahmad; Lesani, Seyyed Mohammad; Abolhasani, Marziyeh; Hashemzadeh Chaleshtori, Morteza

    2013-01-01

    Hearing loss (HL) is the most frequent sensory defect affecting 1 in 1000 neonates. This can occur due to genetic or environmental causes or both. The genetic causes are very heterogenous and over 100 loci have been identified to cause autosomal recessive non - syndromic hearing loss (ARNSHL). The aim of this study was to determine the contribution of the LRTOMT gene mutations in causing ARNSHL. One hundred fifty seven pupils affected with ARNSHL from Azarbaijan Sharghi, Kordestan, Gilan and Golestan provinces, north and west of Iran, were ascertained. In this descriptive - laboratory study, the presence of LRTOMT mutations were initially checked using PCR – Single - strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) strategy. Samples with shifted bands on the gel were confirmed by DNA sequencing method. The PCR-SSCP/HA and the subsequent direct DNA sequencing showed no mutation in the population studied. We conclude that LRTOMT mutations have no role in causing sporadic deafness in the studied population. Further studies on other populations and samples could clarify the exact role of LRTOMT mutations. PMID:24551789

  2. Investigation of LRTOMT gene (locus DFNB63) mutations in Iranian patients with autosomal recessive non-syndromic hearing loss.

    PubMed

    Taghizadeh, Seyyed Hossein; Kazeminezhad, Seyyed Reza; Sefidgar, Seyyed Ali Asghar; Yazdanpanahi, Nasrin; Tabatabaeifar, Mohammad Amin; Yousefi, Ahmad; Lesani, Seyyed Mohammad; Abolhasani, Marziyeh; Hashemzadeh Chaleshtori, Morteza

    2013-01-01

    Hearing loss (HL) is the most frequent sensory defect affecting 1 in 1000 neonates. This can occur due to genetic or environmental causes or both. The genetic causes are very heterogenous and over 100 loci have been identified to cause autosomal recessive non - syndromic hearing loss (ARNSHL). The aim of this study was to determine the contribution of the LRTOMT gene mutations in causing ARNSHL. One hundred fifty seven pupils affected with ARNSHL from Azarbaijan Sharghi, Kordestan, Gilan and Golestan provinces, north and west of Iran, were ascertained. In this descriptive - laboratory study, the presence of LRTOMT mutations were initially checked using PCR - Single - strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) strategy. Samples with shifted bands on the gel were confirmed by DNA sequencing method. The PCR-SSCP/HA and the subsequent direct DNA sequencing showed no mutation in the population studied. We conclude that LRTOMT mutations have no role in causing sporadic deafness in the studied population. Further studies on other populations and samples could clarify the exact role of LRTOMT mutations.

  3. The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

    PubMed

    Zazo Seco, Celia; Wesdorp, Mieke; Feenstra, Ilse; Pfundt, Rolph; Hehir-Kwa, Jayne Y; Lelieveld, Stefan H; Castelein, Steven; Gilissen, Christian; de Wijs, Ilse J; Admiraal, Ronald Jc; Pennings, Ronald Je; Kunst, Henricus Pm; van de Kamp, Jiddeke M; Tamminga, Saskia; Houweling, Arjan C; Plomp, Astrid S; Maas, Saskia M; de Koning Gans, Pia Am; Kant, Sarina G; de Geus, Christa M; Frints, Suzanna Gm; Vanhoutte, Els K; van Dooren, Marieke F; van den Boogaard, Marie-José H; Scheffer, Hans; Nelen, Marcel; Kremer, Hannie; Hoefsloot, Lies; Schraders, Margit; Yntema, Helger G

    2017-02-01

    Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes. Two hundred index patients, mostly of Dutch origin, with presumed hereditary HI underwent WES followed by targeted analysis of an HI gene panel of 120 genes. We found causative variants underlying the HI in 67 of 200 patients (33.5%). Eight of these patients have a large homozygous deletion involving STRC, OTOA or USH2A, which could only be identified by copy number variation detection. Variants of uncertain significance were found in 10 patients (5.0%). In the remaining 123 cases, no potentially causative variants were detected (61.5%). In our patient cohort, causative variants in GJB2, USH2A, MYO15A and STRC, and in MYO6 were the leading causes for autosomal recessive and dominant HI, respectively. Segregation analysis and functional analyses of variants of uncertain significance will probably further increase the diagnostic yield of WES.

  4. Hearing Aids

    MedlinePlus

    ... more in both quiet and noisy situations. Hearing aids help people who have hearing loss from damage ... your doctor. There are different kinds of hearing aids. They differ by size, their placement on or ...

  5. Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene

    PubMed Central

    Wong, Swee-Hee; Wang, Wen-Hung; Chen, Pin-Hua; Li, Shuan-Yow; Yang, Jiann-Jou

    2017-01-01

    In a previous study, we identified a novel missense mutation, p.W77S, in the GJC3 gene encoding connexin30.2/connexin31.3 (CX30.2/CX31.3) from patients with hearing loss. The functional alteration of CX30.2/CX31.3 caused by the p.W77S mutant of GJC3 gene, however, remains unclear. In the current study, our result indicated that the p.W77 is localized at the second membrane-spanning segments (TM2) and near border of the E1 domain of the CX30.2/CX31.3 protein and highly conserved (Conseq score = 8~9) in all species. The p.W77S missense mutation proteins in the intracellular distribution are different CX30.2/CX31.3WT and an accumulation of the mutant protein in the endoplasmic reticulum (ER) of the HeLa cell. Furthermore, co-expression of WT and p.W77S mutant chimerae proteins showed that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the WT proteins' expression in the cell membranes. In addition, we found that CX30.2/CX31.3W77S missense mutant proteins were degraded by lysosomes and proteosomes in the transfected HeLa cell. Based on these findings, we suggest that p.W77S mutant has a dominant negative effect on the formation and function of the gap junction. These results give a novel molecular elucidation for the mutation of GJC3 in the development of hearing loss. PMID:28367085

  6. Parallel evolution of auditory genes for echolocation in bats and toothed whales.

    PubMed

    Shen, Yong-Yi; Liang, Lu; Li, Gui-Sheng; Murphy, Robert W; Zhang, Ya-Ping

    2012-06-01

    The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators--two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function.

  7. Parallel Evolution of Auditory Genes for Echolocation in Bats and Toothed Whales

    PubMed Central

    Li, Gui-Sheng; Murphy, Robert W.; Zhang, Ya-Ping

    2012-01-01

    The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators—two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function. PMID:22761589

  8. Screening for gap junction protein beta-2 gene mutations in Malays with autosomal recessive, non-syndromic hearing loss, using denaturing high performance liquid chromatography.

    PubMed

    Aishah, Z Siti; Khairi, M D Mohd; Normastura, A R; Zafarina, Z; Zilfalil, B A

    2008-12-01

    To determine the frequency and type of gap junction protein beta-2 gene mutations in Malay patients with autosomal recessive, non-syndromic hearing loss. A total of 33 Malay patients with autosomal recessive, non-syndromic hearing loss were screened for mutations in the Cx26 coding region. Deoxyribonucleic acid was extracted from buccal swab samples and subjected to polymerase chain reaction. Slow-reannealing was performed, followed by screening using denaturing high performance liquid chromatography. Eight of the samples (24.2 per cent) showed heterozygous peaks, and further sequencing of these samples revealed four patients (50.0 per cent) with the W24X mutation, two (25.0 per cent) with the V37I mutation and another two (25.0 per cent) with the G4D mutation. Analysis of buccal swab samples by denaturing high performance liquid chromatography is noninvasive and suitable for rapid and reliable screening of gap junction protein beta-2 gene mutations in patients with autosomal recessive, non-syndromic hearing loss. Malay patients with autosomal recessive, non-syndromic hearing loss have different kinds of gap junction protein beta-2 gene mutations which are rarely found in other populations.

  9. Molecular biology of hearing

    PubMed Central

    Stöver, Timo; Diensthuber, Marc

    2012-01-01

    The inner ear is our most sensitive sensory organ and can be subdivided into three functional units: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound, which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear houses the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In recent years there has been significant progress in research on the molecular basis of hearing. An increasing number of genes and proteins related to hearing are being identified and characterized. The growing knowledge of these genes contributes not only to greater appreciation of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss. PMID:22558056

  10. [Audiologic and molecular screening for hearing loss by 35delG mutation in connexin 26 gene and congenital cytomegalovirus infection].

    PubMed

    Streitenberger, Edgardo Raúl; Suárez, Ariel Ignacio; Masciovecchio, María Verónica; Laurnagaray, Diana; Alda, Ernesto

    2011-12-01

    Hearing loss may be attributed to genetic and environmental factors. Mutations in the gene of the CX26 protein (connexin 26), are responsible for 30-80% of all cases of non-syndromic profound hearing loss. The 35delG is the most frequent variant in the caucasian population. As to environmental factors, the cytomegalovirus (CMV) is the main cause of congenital infection. To determine the prevalence of congenital CMV infection and the frequency of the 35delG mutation in newborns. To identify those at risk of suffering hearing loss in order to do an audiologic follow-up of detected cases. One thousand and twenty samples of dry blood spots corresponding to newborns were tested using conventional and real time PCR. Audiologic screening was performed to all newborns before hospital discharge. Fifteen out of 1020 subjects were heterozygous for the mutation. No homozygous patients were found. Six out of the samples tested positive for CMV (confirmed by a urine sample), out of which only one newborn was symptomatic. The auditory brainstem response was recorded in all these children. Hearing loss was found in three children with congenital CMV infection and two with 35delG mutation. The frecuency of 35delG mutation carriers in our population was 1.3% and the CMV congenital infection prevalence was 0.6%. Audiologic monitoring of these two populations allowed detection of hearing loss of late onset.

  11. [Hereditary hearing loss: Part 2: Syndromic forms of hearing loss].

    PubMed

    Burke, W F; Lenarz, T; Maier, H

    2014-10-01

    Syndromic hearing loss is responsible for approximately 30% of cases of inherited hearing loss. The syndromic form can be differentiated from nonsyndromic hearing loss by the presence of associated symptoms in other organ systems. While for many forms of syndromic hearing loss the individual genes responsible have been identified, the etiology of other associated symptoms remains unclear. The role of the ENT physician is to select appropriate clinical and genetic diagnostic tools based on the presentation of the patient and to subsequently initiate and perform the required hearing loss therapy.

  12. Hearing Screening

    ERIC Educational Resources Information Center

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  13. Hearing Screening

    ERIC Educational Resources Information Center

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  14. Mutations in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene cause autosomal recessive nonsyndromic hearing loss.

    PubMed

    Kalay, Ersan; Li, Yun; Uzumcu, Abdullah; Uyguner, Oya; Collin, Rob W; Caylan, Refik; Ulubil-Emiroglu, Melike; Kersten, Ferry F J; Hafiz, Gunter; van Wijk, Erwin; Kayserili, Hulya; Rohmann, Edyta; Wagenstaller, Janine; Hoefsloot, Lies H; Strom, Tim M; Nürnberg, Gudrun; Baserer, Nermin; den Hollander, Anneke I; Cremers, Frans P M; Cremers, Cor W R J; Becker, Christian; Brunner, Han G; Nürnberg, Peter; Karaguzel, Ahmet; Basaran, Seher; Kubisch, Christian; Kremer, Hannie; Wollnik, Bernd

    2006-07-01

    In two large Turkish consanguineous families, a locus for autosomal recessive nonsyndromic hearing loss (ARNSHL) was mapped to chromosome 6p21.3 by genome-wide linkage analysis in an interval overlapping with the loci DFNB53 (COL11A2), DFNB66, and DFNB67. Fine mapping excluded DFNB53 and subsequently homozygous mutations were identified in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene, also named tetraspan membrane protein of hair cell stereocilia (TMHS) gene, which was recently shown to be mutated in the "hurry scurry" mouse and in two DFNB67-linked families from Pakistan. In one family, we found a homozygous one-base pair deletion, c.649delG (p.Glu216ArgfsX26) and in the other family we identified a homozygous transition c.494C>T (p.Thr165Met). Further screening of index patients from 96 Turkish ARNSHL families and 90 Dutch ARNSHL patients identified one additional Turkish family carrying the c.649delG mutation. Haplotype analysis revealed that the c.649delG mutation was located on a common haplotype in both families. Mutation screening of the LHFPL5 homologs LHFPL3 and LHFPL4 did not reveal any disease causing mutation. Our findings indicate that LHFPL5 is essential for normal function of the human cochlea.

  15. A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

    PubMed Central

    van Wijk, E; Krieger, E; Kemperman, M; De Leenheer, E M R; Huygen, P; Cremers, C; Cremers, F; Kremer, H

    2003-01-01

    Linkage analysis in a multigenerational family with autosomal dominant hearing loss yielded a chromosomal localisation of the underlying genetic defect in the DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the γ-1-actin (ACTG1) gene, which was considered an attractive candidate gene because actins are important structural elements of the inner ear hair cells. In this study, a Thr278Ile mutation was identified in helix 9 of the modelled protein structure. The alteration of residue Thr278 is predicted to have a small but significant effect on the γ 1 actin structure owing to its close proximity to a methionine residue at position 313 in helix 11. Met313 has no space in the structure to move away. Moreover, the Thr278 residue is highly conserved throughout eukaryotic evolution. Using a known actin structure the mutation could be predicted to impair actin polymerisation. These findings strongly suggest that the Thr278Ile mutation in ACTG1 represents the first disease causing germline mutation in a cytoplasmic actin isoform. PMID:14684684

  16. Genetics Home Reference: nonsyndromic hearing loss

    MedlinePlus

    ... age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs ... or Free article on PubMed Central GeneReview: Deafness and Hereditary ...

  17. Association between the methylenetetrahydrofolate reductase gene C677T polymorphism and sudden sensorineural hearing loss: a meta-analysis.

    PubMed

    Shu, Jingcheng; Yin, Shihua; Tan, An-Zhou; He, Meirong

    2015-09-01

    A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and sudden sensorineural hearing loss (SSNHL), but the results were inconsistent. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with SSNHL. A systematic literature search of the associated studies up to May 1, 2014, was conducted using the following electronic databases: PubMed, Embase, Medline, and the China National Knowledge Infrastructure. Statistical analyses were performed by STATA12.0 software, with odds ratios (ORs) and their 95 % confidence intervals (CIs). Six eligible studies including covering 1,271 objects were identified. A pooled analysis of these studies showed no significant association between C677T polymorphism and risk of SSNHL: T vs. C (OR = 1.334, POR = 0.105); TT vs. CC (OR = 1.580, POR = 0.231); CT vs. CC (OR = 1.500, POR = 0.123); TT vs. CC + CT (OR = 1.326, POR = 0.293); and TT + CT vs. CC (OR = 1.540, POR = 0.102). But in subgroup analysis, a significant association was found in European populations (T vs. C, OR = 1.542, 95 % CI 1.008-2.359, P = 0.046; TT vs. CT + CC, OR = 1.856, 95 % CI 1.245-2.767, P = 0.002). There was no significant association in any model in the Asian populations. The present meta-analysis suggests that MTHFR gene C677T polymorphism is significantly associated with increased risk of SSNHL disease in European populations, but no statistically significant association was found between the MTHFR C677T gene mutation and SSNHL in Asian. Further large and well-designed studies are needed to confirm this association.

  18. Mutation Screening of Exons 7 and 13 of the TMC1 Gene in Autosomal Recessive Non-syndromic Hearing Loss (ARNSHL) in Iran

    PubMed Central

    Moradipour, Negar; Ghasemi-Dehkordi, Payam; Heibati, Fatemeh; Parchami-Barjui, Shahrbanuo; Abolhasani, Marziyeh; Rashki, Ahmad; Hashemzadeh-Chaleshtori, Morteza

    2016-01-01

    Background: Non-syndromic hearing loss (NSHL) is the most common birth defect and occurs in approximately 1/1,000 newborns. NSHL is a heterogeneous trait and can arise due to both genetic and environmental factors. Mutations of the transmembrane channel-like 1 (TMC1) gene cause non-syndromic deafness in humans and mice. Objectives: The aim of the present study was to investigate the association of TMC1 gene mutations of the locus DFNB7/11 in exons 7 and 13 in a cohort of 100 patients with hearing loss in Iran using polymerase chain reaction–single-stranded conformation polymorphism (PCR-SSCP), heteroduplex analysis (HA), and DNA sequencing. Patients and Methods: In this experimental study, the blood samples of 100 NSHL patients were collected from 10 provinces in Iran. These patients had a mean age of 16.5 ± 2.01 years and 74.15% of their parents had consanguinity. DNA was extracted from specimens and mutations of exons 7 and 13 of the TMC1 gene were investigated using PCR-SSCP. All samples were checked via HA reaction and suspected specimens with shift bands were subjected to DNA sequencing for investigation of any gene variation. Results: In this study, no mutation was found in the two exons of TMC1 gene. It was concluded from these results that mutations of the TMC1 gene’s special exons 7 and 13 have a low contribution in patients and are not great of clinical importance in these Iranian provinces. Conclusions: More studies are needed to investigate the relationship between other parts of this gene with hearing loss in different populations through the country. More research could clarify the role of this gene and its relation with deafness and provide essential information for the prevention and management of auditory disorders caused by genetic factors in the Iranian population. PMID:27247785

  19. Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India.

    PubMed

    Adhikary, Bidisha; Ghosh, Sudakshina; Paul, Silpita; Bankura, Biswabandhu; Pattanayak, Arup Kumar; Biswas, Subhradev; Maity, Biswanath; Das, Madhusudan

    2015-12-01

    Genetically caused nonsyndromic hearing loss is highly heterogeneous. Inspite of this large heterogeneity, mutations in the genes GJB2, GJB6 and SLC26A4 are major contributors. The mutation spectrum of these genes varies among different ethnic groups. Only a handful of studies focused on the altered genetic signature of these genes in different demographic regions of India but never focused on the eastern part of the country. Our study for the first time aimed to characterize the mutation profile of these genes in hearing loss patients of West Bengal state, India. Mutations in GJB2, GJB6 and SLC26A4 genes were screened by bidirectional sequencing from 215 congenital nonsyndromic hearing loss patients. Radiological diagnosis was performed in patients with SLC26A4 mutations by temporal bone CT scan. The study revealed that 4.65% and 6.97% patients had monoallelic and biallelic GJB2 mutations respectively. Six mutations were identified, p.W24X being the most frequent one accounting for 71.05% of the mutated alleles. Mutations in GJB6 including the previously identified deletion mutation (GJB6-D13S1830) were not identified in our study. Further, no patients harbored biallelic mutations in the SLC26A4 gene or the common inner ear malformation Enlarged Vestibular Aqueduct (EVA). The mutation profile of GJB2 in our study is distinct from other parts of India, suggesting that the mutation spectrum of this gene varies with ethnicity and geographical origin. The absence of GJB6 mutations and low frequency of SLC26A4 mutations suggest that additional genetic factors may also contribute to this disease.

  20. Duplicated genes with split functions: independent roles of protocadherin15 orthologues in zebrafish hearing and vision.

    PubMed

    Seiler, Christoph; Finger-Baier, Karin C; Rinner, Oliver; Makhankov, Yuri V; Schwarz, Heinz; Neuhauss, Stephan C F; Nicolson, Teresa

    2005-02-01

    In the sensory receptors of both the eye and the ear, specialized apical structures have evolved to detect environmental stimuli such as light and sound. Despite the morphological divergence of these specialized structures and differing transduction mechanisms, the receptors appear to rely in part on a shared group of genes for function. For example, mutations in Usher (USH) genes cause a syndrome of visual and acoustic-vestibular deficits in humans. Several of the affected genes have been identified, including the USH1F gene, which encodes protocadherin 15 (PCDH15). Pcdh15 mutant mice also have both auditory and vestibular defects, although visual defects are not evident. Here we show that zebrafish have two closely related pcdh15 genes that are required for receptor-cell function and morphology in the eye or ear. Mutations in pcdh15a cause deafness and vestibular dysfunction, presumably because hair bundles of inner-ear receptors are splayed. Vision, however, is not affected in pcdh15a mutants. By contrast, reduction of pcdh15b activity using antisense morpholino oligonucleotides causes a visual defect. Optokinetic and electroretinogram responses are reduced in pcdh15b morpholino-injected larvae. In electron micrographs, morphant photoreceptor outer segments are improperly arranged, positioned perpendicular to the retinal pigment epithelium and are clumped together. Our results suggest that both cadherins act within their respective transduction organelles: Pcdh15a is necessary for integrity of the stereociliary bundle, whereas Pcdh15b is required for alignment and interdigitation of photoreceptor outer segments with the pigment epithelium. We conclude that after a duplication of pcdh15, one gene retained an essential function in the ear and the other in the eye.

  1. Hearing Aids

    MedlinePlus

    ... hearing aid has three basic parts: a microphone, amplifier, and speaker. The hearing aid receives sound through ... to electrical signals and sends them to an amplifier. The amplifier increases the power of the signals ...

  2. Hearing Aids

    MedlinePlus

    ... use by people with hearing loss, and sound amplifiers for consumers with no hearing loss who want ... are medical devices, it does not consider sound amplifiers to be medical devices when labeled for recreational ...

  3. Hearing Loss

    MedlinePlus

    ... earphone in your baby’s ear. The earphone is connected to a computer. Your baby’s provider sends a ... treatment can help children with hearing loss develop speech, language and social skills. Without early treatment, hearing ...

  4. Hearing regulates Drosophila aggression

    PubMed Central

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C.; Heinrich, Ralf; Callaerts, Patrick

    2017-01-01

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly’s auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level. PMID:28115690

  5. Hearing regulates Drosophila aggression.

    PubMed

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

    2017-02-21

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

  6. Nanotechnology in Auditory Research: Membrane Electromechanics in Hearing

    PubMed Central

    Araya, Mussie; Brownell, William E.

    2016-01-01

    The soft, thin membranes that envelop all living cells are 2D, nanoscale, fluid assemblies of phospholipids, sterols, proteins and other molecules. Mechanical interactions between these components facilitate membrane function, a key example of which is ion flow mediated by the mechanical opening and closing of channels. Hearing and balance are initiated by the modulation of ion flow through mechanoreceptor channels in stereocilia membranes. Cochlear amplification by the outer hair cell involves modulation of ion movement by the membrane protein prestin. Voltage gated ion channels shape the receptor potential in hair cells and are responsible for the initiation of action potentials that are at the heart of sensory processing in the brain. All three processes require a membrane and their kinetics are modulated by the mechanical (ie. material) properties of the membrane. This chapter reviews the methodology for measuring the mechanics of cellular membranes and introduces a method for examining membrane electromechanics. The approach allows examination of electromechanically mediated interactions between the different molecular species in the membrane that contribute to the biology of hearing and balance. PMID:27259937

  7. Gene-gene interaction of GJB2, SOD2, and CAT on occupational noise-induced hearing loss in Chinese Han population.

    PubMed

    Wang, Sheng Li; Yu, Lu Gang; Liu, Ren Ping; Zhu, Wan Zhan; Gao, Wei Min; Xue, Li Ping; Jiang, Xu; Zhang, Ya Han; Yi, Ding; Chen, Dong; Zhang, Yong Hong

    2014-12-01

    The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.

  8. Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNA{sup Ser(UCN)} genes in two Chinese families

    SciTech Connect

    Zhu Yi; Liao Zhisu; Li Zhiyuan; Chen Jianfu; Qian Yaping; Tang Xiaowen; Wang Jindan; Yang Li; Li Ronghua; Ji Jinzhang; Choo, Daniel I. |; Lu Jianxin . E-mail: jx@mail.wz.zj.cn; Guan Minxin |||. E-mail: min-xin.guan@chmcc.org

    2006-04-14

    We report here the clinical, genetic, and molecular characterization of two Chinese families with aminoglycoside induced and non-syndromic hearing impairment. Clinical and genetic evaluations revealed the variable severity and age-of-onset in hearing impairment in these families. Strikingly, there were extremely low penetrances of hearing impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G7444A mutation associated with hearing loss. Indeed, the G7444A mutation in the CO1 gene and the precursor of tRNA{sup Ser(UCN)} gene is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. Their mitochondrial genomes belong to the Eastern Asian haplogroups C5a and D4a, respectively. In fact, the occurrence of the G7444A mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. However, there was the absence of other functionally significant mtDNA mutations in two Chinese pedigrees carrying the G7444A mutation. Therefore, nuclear modifier gene(s) or aminoglycoside(s) may play a role in the phenotypic expression of the deafness-associated G7444A mutation in these Chinese pedigrees.

  9. Adaptive evolution of tight junction protein claudin-14 in echolocating whales.

    PubMed

    Xu, Huihui; Liu, Yang; He, Guimei; Rossiter, Stephen J; Zhang, Shuyi

    2013-11-10

    Toothed whales and bats have independently evolved specialized ultrasonic hearing for echolocation. Recent findings have suggested that several genes including Prestin, Tmc1, Pjvk and KCNQ4 appear to have undergone molecular adaptations associated with the evolution of this ultrasonic hearing in mammals. Here we studied the hearing gene Cldn14, which encodes the claudin-14 protein and is a member of tight junction proteins that functions in the organ of Corti in the inner ear to maintain a cationic gradient between endolymph and perilymph. Particular mutations in human claudin-14 give rise to non-syndromic deafness, suggesting an essential role in hearing. Our results uncovered two bursts of positive selection, one in the ancestral branch of all toothed whales and a second in the branch leading to the delphinid, phocoenid and ziphiid whales. These two branches are the same as those previously reported to show positive selection in the Prestin gene. Furthermore, as with Prestin, the estimated hearing frequencies of whales significantly correlate with numbers of branch-wise non-synonymous substitutions in Cldn14, but not with synonymous changes. However, in contrast to Prestin, we found no evidence of positive selection in bats. Our findings from Cldn14, and comparisons with Prestin, strongly implicate multiple loci in the acquisition of echolocation in cetaceans, but also highlight possible differences in the evolutionary route to echolocation taken by whales and bats.

  10. Correspondence regarding Ballana et al., "Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment".

    PubMed

    Abreu-Silva, R S; Batissoco, A C; Lezirovitz, K; Romanos, J; Rincon, D; Auricchio, M T B M; Otto, P A; Mingroni-Netto, R C

    2006-05-12

    Ballana et al. [E. Ballana, E. Morales, R. Rabionet, B. Montserrat, M. Ventayol, O. Bravo, P. Gasparini, X. Estivill, Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment, Biochem. Biophys. Res. Commun. 341 (2006) 950-957] detected a T1291C mutation segregating in a Cuban pedigree with hearing impairment. They interpreted it as probably pathogenic, based on family history, RNA conformation prediction and its absence in a control group of 95 Spanish subjects. We screened a sample of 203 deaf subjects and 300 hearing controls (110 "European-Brazilians" and 190 "African-Brazilians") for the mitochondrial mutations A1555G and T1291C. Five deaf subjects had the T1291C substitution, three isolated cases and two familial cases. In the latter, deafness was paternally inherited or segregated with the A1555G mutation. This doesn't support the hypothesis of T1291C mutation being pathogenic. Two "African-Brazilian" controls also had the T1291C substitution. Six of the seven T1291C-carriers (five deaf and two controls) had mitochondrial DNA of African origin, belonging to macrohaplogroup L1/L2. Therefore, these data point to T1291C substitution as most probably an African non-pathogenic polymorphism.

  11. Localization of a Gene for Autosomal Recessive Distal Renal Tubular Acidosis with Normal Hearing (rdRTA2) to 7q33-34

    PubMed Central

    Karet, Fiona E.; Finberg, Karin E.; Nayir, Ahmet; Bakkaloglu, Aysin; Ozen, Seza; Hulton, Sally A.; Sanjad, Sami A.; Al-Sabban, Essam A.; Medina, Juan F.; Lifton, Richard P.

    1999-01-01

    Summary Failure of distal nephrons to excrete excess acid results in the “distal renal tubular acidoses” (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing. PMID:10577919

  12. Mutation in the Hair Cell Specific Gene POU4F3 Is a Common Cause for Autosomal Dominant Nonsyndromic Hearing Loss in Chinese Hans

    PubMed Central

    He, Longxia; Pang, Xiuhong; Chen, Penghui

    2016-01-01

    Autosomal dominant nonsyndromic hearing loss (ADNSHL) is extremely heterogeneous. So far the genetic etiological contribution of the gene POU4F3 associated with ADNSHL has been rarely reported. In our previous study, a c.603_604delGG mutation in the hair cell specific gene POU4F3 has been identified as the pathogenic cause in one of the seven Chinese Han ADNSHL families. In the present study, we performed targeted next-generation sequencing of 144 known deafness genes in another nine Chinese Han ADNSHL families and identified two more novel mutations in POU4F3, p.Leu311Pro and c.120+1G>C, as the pathogenic cause. Clinical characterization of the affected individuals in these three families showed that the three POU4F3 mutations may lead to progressive hearing loss with variable ages of onset and degrees of severity. Our results suggested that mutations in POU4F3 are a relatively common cause (3/16) for ADNSHL in Chinese Hans, which should be routinely screened in such cases during genetic testing. PMID:28053790

  13. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome

    PubMed Central

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-01-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1−/− mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0–P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner’s membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1−/− mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. PMID:26084842

  14. Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment

    PubMed Central

    Falah, Masoumeh; Najafi, Mohammad; Houshmand, Massoud; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. PMID:27555755

  15. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

    PubMed

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-08-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss.

  16. Types of Hearing Aids

    MedlinePlus

    ... Devices Consumer Products Hearing Aids Types of Hearing Aids Share Tweet Linkedin Pin it More sharing options ... some features for hearing aids? What are hearing aids? Hearing aids are sound-amplifying devices designed to ...

  17. Do Hearing Protectors Protect Hearing?

    PubMed Central

    Groenewold, Matthew R.; Masterson, Elizabeth A.; Themann, Christa L.; Davis, Rickie R.

    2015-01-01

    Background We examined the association between self-reported hearing protection use at work and incidence of hearing shifts over a 5-year period. Methods Audiometric data from 19,911 workers were analyzed. Two hearing shift measures—OSHA standard threshold shift (OSTS) and high-frequency threshold shift (HFTS)—were used to identify incident shifts in hearing between workers’ 2005 and 2009 audiograms. Adjusted odds ratios were generated using multivariable logistic regression with multi-level modeling. Results The odds ratio for hearing shift for workers who reported never versus always wearing hearing protection was nonsignificant for OSTS (OR 1.23, 95% CI 0.92–1.64) and marginally significant for HFTS (OR 1.26, 95% CI 1.00–1.59). A significant linear trend towards increased risk of HFTS with decreased use of hearing protection was observed (P = 0.02). Conclusion The study raises concern about the effectiveness of hearing protection as a substitute for noise control to prevent noise-induced hearing loss in the workplace. Am. J. Ind. Med. 57:1001–1010, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. PMID:24700499

  18. Functional variants of MIF, INFG and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with Ménière's disease.

    PubMed

    Gázquez, Irene; Moreno, Antonia; Requena, Teresa; Ohmen, Jeff; Santos-Perez, Sofia; Aran, Ismael; Soto-Varela, Andres; Pérez-Garrigues, Herminio; López-Nevot, Alicia; Batuecas, Angel; Friedman, Rick A; López-Nevot, Miguel A; López-Escamez, Jose A

    2013-03-01

    Variability in acute immune response genes could determine susceptibility or prognosis for Ménière's disease (MD). The cytokines tumor necrosis factor α (TNFα), macrophage migration inhibitory factor (MIF) and interferon γ (INFγ) are proinflammatory cytokines of the innate immune response. These cytokines mediate inflammation and have been previously associated with the inflammatory process in several autoimmune diseases. We investigated the association between functional allelic variants of MIF (rs35688089), IFNG (rs2234688) and TNFA (rs1800629) in patients with MD. In addition to testing these variants for an association with disease, we also tested for an association with clinical aspects of disease progression, such as persistence of vertigo and the sensorineural hearing loss. A total of 580 patients with diagnosis of definite MD, according to the diagnostic scale of the American Academy of Otolaryngology-Head and Neck Surgery, and 552 healthy controls were included. DNA samples from a set of 291 American patients were used to confirm the results obtained in the MIF gene in our Spanish cohort. Although we found a significant association with the allele containing five repeats of CATT within the MIF gene in patients with MD in the Spanish cohort [corrected p = 0.008, OR = 0.69 (95 % CI, 0.54-0.88)], this finding could not be replicated in the American set. Moreover, no genetic associations for variants in either the TNFA or IFNG genes and MD were found. These results support the conclusion that functional variants of MIF, INFG, and TFNA genes are not associated with disease susceptibility or hearing loss progression in patients with MD.

  19. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    Astrophysicist, American Museum of Natural History and Director, Hayden Planetarium Dr. Neil deGrasse Tyson testifies during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. NASA Administrator Charles Bolden testified at the same hearing prior to Tyson. Photo Credit: (NASA/Bill Ingalls)

  20. Functional analysis of a novel I71N mutation in the GJB2 gene among Southern Egyptians causing autosomal recessive hearing loss.

    PubMed

    Mohamed, Mostafa R; Alesutan, Ioana; Föller, Michael; Sopjani, Mentor; Bress, Andreas; Baur, Manuela; Salama, Ragaa H M; Bakr, Mohamed S; Mohamed, Mohamed A; Blin, Nikolaus; Lang, Florian; Pfister, Markus

    2010-01-01

    Mutations in GJB2, a gene encoding the gap junction protein connexin 26 (Cx26), are a major cause for inherited and sporadic non-syndromic hearing loss, albeit with highly variable clinical effects. To determine new mutations and their frequencies in a Southern Egyptian population restriction fragment length polymorphism, gene sequencing, and single strand conformational polymorphism revealed only 2 mutations for GJB2: c.35delG and p.I71N. The allelic frequency of the c.35delG mutation was 8.7% (found in 27 out of 310 investigated alleles) resulting in a relatively low carrier frequency (1.6%) in Upper Egypt. The new mutation, a substitution of isoleucin (I) (a non-polar amino acid) by the polar amino acid asparagin (N), was localized within the conserved Cx26 structure. The functional significance of p.I71N was tested by injection of cRNA into Xenopus laevis oocytes. Cx26 hemi-channel activity was measured by depolarization activated conductance in non-coupled oocytes. As a result, the p.I71N mutated channel was non-functional. The study discloses a novel, functionally relevant GJB2 mutation and defines the contribution of Cx26 alterations to the hearing loss in the Southern Egyptian population.

  1. Analysis of gene polymorphisms associated with K ion circulation in the inner ear of patients susceptible and resistant to noise-induced hearing loss.

    PubMed

    Pawelczyk, Malgorzata; Van Laer, Lut; Fransen, Erik; Rajkowska, Elzbieta; Konings, Annelies; Carlsson, Per-Inge; Borg, Erik; Van Camp, Guy; Sliwinska-Kowalska, Mariola

    2009-07-01

    Noise-induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise-exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we replicated associations that were previously reported in a Swedish sample set, hence confirming that they are NIHL susceptibility genes. Additionally we report significant associations in GJB1, GJB2, GJB4, KCNJ10 and KCNQ1, however due to the lack of replication in the Swedish sample set, these results should be seen as suggestive.

  2. [Congenital hearing loss in children. 2: Genetic hearing loss].

    PubMed

    Gross, M; Lange, K; Spormann-Lagodzinski, M

    2001-08-01

    Molecular genetic tests enable a differentiated view of patho-physiological correlation of sensori-neural hearing impairment. On the basis of 4791 records of the German Central Registry on Childhood Hearing Loss (Deutsches Zentralregister für kindliche Hörstörungen (DZH)) it was shown that 35% of all permanent hearing impairment in Germany is caused genetically and 20% are acquired. The proportion of indistinct etiology remains at 45%. The number of children who have a hearing impairment by birth is also vague. It has to be expected that approximately 5% of these children develop a hearing impairment afterwards albeit its genetic determination. In 4791 cases a syndromal phenotype was assumed in 8.9%. Practical advice is given for clinical routine diagnostics with pragmatic suggestions and some distinct syndromes are described. Hitherto identified deafness genes reveal their role in pathological auditory function. Future diagnostic and therapeutic strategies are outlined on the basis of molecular genetic methods.

  3. [Investigation into the relationship between mitochondrial 12 S rRNA gene, tRNA gene and cytochrome oxidase Ⅱ gene variations and the risk of noise-induced hearing loss].

    PubMed

    Jiao, J; Gu, G Z; Chen, G S; Li, Y H; Zhang, H L; Yang, Q Y; Xu, X R; Zhou, W H; Wu, H; He, L H; Zheng, Y X; Yu, S F

    2017-01-06

    Objective: To explore the relationship between mitochondrial 12 S rRNA gene variation, tRNA gene variation and cytochrome oxidase Ⅱ gene point mutations and the risk of noise-induced hearing loss (NIHL). Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory in Henan province, China, from January 1, 2006 to December 31, 2015. Subjects whose average hearing threshold was more than 40 dB(A) in high frequency were defined as the case group, and subjects whose average hearing threshold was less than 35 dB(A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. Subjects was recruited into the case group (n=286) and the control group (n=286) according to gender, age, job category and time of exposure to noise, and a 1∶1 case-control study was carried out. We genotyped eight single nucleotide polymorphisms in the mitochondrial 12 S rRNA gene, the mitochondrial tRNA gene and the mitochondrial cytochrome oxidase Ⅱ gene using SNPscan high-throughput genotyping technology from the recruited subjects. The relationship between polymorphic sites and NIHL, adjusted for covariates, was analyzed using conditional logistic regression analysis, as were the subgroup data. Results: The average age of the recruited subjects was (40.3±8.1) years and the length of service exposure to noise was (18.6±8.9) years. The range of noise exposed levels and cumulative noise exposure (CNE) was 80.1- 93.4 dB (A) and 86.8- 107.9 dB (A) · year, respectively. For workers exposed to noise at a CNE level<98 dB (A) · year, smokers showed an increased risk of NIHL of 1.88 (1.16-3.05) compared with non-smokers; for workers exposed to noise at a CNE level ≥98 dB(A) · year, smokers showed an increased risk of NIHL of 2.53 (1.49- 4.30) compared with non-smokers. For workers exposed to noise at a CNE level<98 dB (A) · year, the results of univariate analysis and multifactor analysis

  4. Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Ménière's disease in a Japanese population.

    PubMed

    Teranishi, Masaaki; Uchida, Yasue; Nishio, Naoki; Kato, Ken; Otake, Hironao; Yoshida, Tadao; Suzuki, Hirokazu; Sone, Michihiko; Sugiura, Saiko; Ando, Fujiko; Shimokata, Hiroshi; Nakashima, Tsutomu

    2012-10-01

    The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that oxidative stress is related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the associations between genetic polymorphisms located in oxidative stress response genes and susceptibility to SSNHL and Ménière's disease. We compared 84 patients affected by SSNHL, 82 patients affected by Ménière's disease, and 2107 adults (1056 men and 1051 women; mean age, 59.2 years; range, 40-79 years) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios for SSNHL and Ménière's disease in individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1) (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu, rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala, rs4880), with adjustment for age and gender. No significant differences in the distribution of the genotypes at these polymorphisms were observed among individuals with SSNHL and Ménière's disease and controls. No significant risk for SSNHL and Ménière's disease was observed in the additive genetic model, regardless of moderating variables. The C allele of SOD2 (rs4880) was more frequent in Ménière's disease cases with a hearing level over 50 dB compared with cases with a hearing level below 50 dB, suggesting that this polymorphism is associated with progression of a hearing loss in Ménière's disease. In conclusion, no significant associations between the polymorphisms of GPX1, PON1, PON2, and SOD2 and risk of SSNHL and Ménière's disease were observed in this Japanese case-control study.

  5. Lack of association between DNMT1 gene polymorphisms and noise-induced hearing loss in a Chinese population.

    PubMed

    Hu, Feifei; Li, Xin; Li, Xiuting; Wang, Meilin; Chu, Haiyan; Liu, Kai; Zhang, Hengdong; Zhang, Zhengdong; Zhu, Baoli

    2013-01-01

    DNA methyltransferase 1 (DNMT1) plays a crucial role in maintaining of methylation and chromatin stability. And mutations in DNMT1 can induce one form of neurodegenerative diseases with dementia and sensorineural hearing loss. To assess whether single nucleotide polymorphisms (SNPs) or haplotypes of DNMT1 are related to noise-induced hearing loss (NIHL) in a Chinese population, we genotyped three functional polymorphisms (rs12984523, rs16999593, and rs2228612) in a case-control study involving 615 NIHL cases and 644 controls. However, no significant association was detected between these three SNPs and NIHL susceptibility in the Chinese population. Our data suggested that the DNMT1 polymorphisms may not contribute to risk of NIHL in the Chinese population.

  6. Potential treatments for genetic hearing loss in humans: current conundrums.

    PubMed

    Minoda, R; Miwa, T; Ise, M; Takeda, H

    2015-08-01

    Genetic defects are a major cause of hearing loss in newborns. Consequently, hearing loss has a profound negative impact on human daily living. Numerous causative genes for genetic hearing loss have been identified. However, presently, there are no truly curative treatments for this condition. There have been several recent reports on successful treatments in mice using embryonic gene therapy, neonatal gene therapy and neonatal antisense oligonucleotide therapy. Herein, we describe state-of-the-art research on genetic hearing loss treatment through gene therapy and discuss the obstacles to overcome in curative treatments of genetic hearing loss in humans.

  7. Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion.

    PubMed

    Samuels, Tina L; Yan, Justin C; Khampang, Pawjai; Dettmar, Peter W; MacKinnon, Alexander; Hong, Wenzhou; Johnston, Nikki; Papsin, Blake C; Chun, Robert H; McCormick, Michael E; Kerschner, Joseph E

    2017-08-01

    Persistent, viscous middle ear effusion in pediatric otitis media (OM) contributes to increased likelihood of anesthesia and surgery, conductive hearing loss, and subsequent developmental delays. Biomarkers of effusion viscosity and hearing loss have not yet been identified despite the potential that such markers hold for targeted therapy and screening. To investigate the association of gel-forming mucins and aquaporin 5 (AQP5) gene expression with inflammation, effusion viscosity, and hearing loss in pediatric OM with effusion (OME). Case-control study of 31 pediatric patients (aged 6 months to 12 years) with OME undergoing tympanostomy tube placement and control individuals (aged 1 to 10 years) undergoing surgery for cochlear implantation from February 1, 2013, through November 30, 2014. Those with 1 or more episodes of OM in the previous 12 months, immunologic abnormality, anatomical or physiologic ear defect, OM-associated syndrome (ie, Down syndrome, cleft palate), chronic mastoiditis, or history of cholesteatoma were excluded from the study. All patients with OME and 1 control were recruited from Children's Hospital of Wisconsin, Milwaukee. The remainder of the controls were recruited from Sick Kids Hospital in Toronto, Ontario, Canada. Two to 3 middle ear biopsy specimens, effusions, and preoperative audiometric data (obtained <3 weeks before surgery) were collected from patients; only biopsy specimens were collected from controls. Expression of the mucin 2 (MUC2), mucin 5AC (MUC5AC), mucin 5B (MUC5B), and AQP5 genes were assayed in middle ear biopsy specimens by quantitative polymerase chain reaction. One middle ear biopsy specimen was sectioned for histopathologic analysis. Reduced specific viscosity of effusions was assayed using rheometry. Of the 31 study participants, 24 patients had OME (mean [SD] age, 50.4 [31.9] months; 15 [62.5%] male; 16 [66.7%] white) and 7 acted as controls (mean [SD] age, 32.6 [24.4] months; 2 [26.6%] male; 6 [85.7%] white

  8. About Hearing

    MedlinePlus

    ... communication development. This includes understanding a) the various components of a typically functioning ear, b) what to ... is first helpful to understand the four major components of the hearing mechanism and their purpose. Outer ...

  9. Hearing Loss

    MedlinePlus

    ... topic was provided by the National Institute on Deafness and Other Communication Disorders Topic last reviewed: December ... a total loss of hearing. It can be hereditary or it can result from disease, trauma, certain ...

  10. Hearing Loss

    MedlinePlus

    ... regular part of the working environment, such as farming, construction or factory work, can lead to damage ... Diagnosis and management. Primary Care: Clinics in Office Practice. 2014;41:19. Weber PC. Etiology of hearing ...

  11. Hearing Aids

    MedlinePlus

    ... hair cells (outer and inner rows). When the vibrations move through this fluid, the tiny outer hair ... ear to the brain. Hearing aids intensify sound vibrations that the damaged outer hair cells have trouble ...

  12. Hearing Impairment

    MedlinePlus

    ... up of invisible waves of energy, causes these vibrations. Hearing begins when sound waves that travel through ... When the eardrum vibrates, the ossicles amplify these vibrations and carry them to the inner ear. The ...

  13. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    NASA Administrator Charles Bolden testifies during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    U.S. Senator Bill Nelson, D-Fla., questions NASA Administrator Charles Bolden during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. House Hearing

    NASA Image and Video Library

    2012-03-07

    Rep. Eddie Bernice Johnson, D-TX, asks a question of NASA Administrator Charles Bolden during a House Science, Space and Technology Committee hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  16. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    NASA Administrator Charles Bolden's cowboy boots are seen as he testifies during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    NASA Administrator Charles Bolden's hands and Naval Academy ring are seen as he testifies during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  18. Fish Hearing.

    ERIC Educational Resources Information Center

    Blaxter, J. H. S.

    1980-01-01

    Provides related information about hearing in fish, including the sensory stimulus of sound in the underwater environment, mechanoreceptors in fish, pressure perception and the swimbladder, specializations in sound conduction peculiar to certain fish families. Includes numerous figures. (CS)

  19. Hearing Aids

    MedlinePlus

    ... case goes behind the ear that holds the electronics that make up the actual hearing aid. It's ... there's a hard plastic case that holds the electronic components, but it's joined to the earmold itself, ...

  20. Apoptosis in acquired and genetic hearing impairment

    PubMed Central

    de Beeck, Ken Op; Schacht, Jochen; Van Camp, Guy

    2012-01-01

    Apoptosis is an important physiological process. Normally, a healthy cell maintains a delicate balance between pro- and anti-apoptotic factors, allowing it to live and proliferate. It is thus not surprising that disturbance of this delicate balance may result in disease. It is a well known fact that apoptosis also contributes to several acquired forms of hearing impairment. Noise-induced hearing loss is the result of prolonged exposure to excessive noise, triggering apoptosis in terminally differentiated sensory hair cells. Moreover, hearing loss caused by the use of therapeutic drugs such as aminoglycoside antibiotics and cisplatin potentially may result in the activation of apoptosis in sensory hair cells leading to hearing loss due to the “ototoxicity” of the drugs. Finally, apoptosis is a key contributor to the development of presbycusis, age-related hearing loss. Recently, several mutations in apoptosis genes were identified as the cause of monogenic hearing impairment. These genes are TJP2, DFNA5 and MSRB3. This implies that apoptosis not only contributes to the pathology of acquired forms of hearing impairment, but also to genetic hearing impairment as well. We believe that these genes constitute a new functional class within the hearing loss field. Here, the contribution of apoptosis in the pathology of both acquired and genetic hearing impairment is reviewed. PMID:21782914

  1. Human radiation, experimentation, ethics, and gene therapy. Hearing before the Subcommittee on Energy of the Committee on Science, Space, and Technology, U.S. House of Representatives, One Hundred Third Congress, Second Session, February 10, 1994

    SciTech Connect

    1994-12-31

    The hearing addressed the human radiation experimentation of the Department of Energy (DOE) and the ethics of such treatment and gene therapy. Historical aspects of these subjects and their contributions to advancing current medical treatments are presented. Statements of officials from government, industry and educational institutions are provided along with documents submitted for the record.

  2. Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA{sup Lys} gene (G8363A)

    SciTech Connect

    Santorelli, F.M.; Mak, Suk-Chun; El-Schahawi, M.

    1996-05-01

    A novel G8363A mutation in the mtDNA tRNA{sup Lys} gene was associated, in two unrelated families, with a syndrome consisting of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. Muscle biopsies from the probands showed mitochondrial proliferation and partial defects of complexes I, III, and IV of the electron-transport chain. The G8363A mutation was very abundant (>95%) in muscle samples from the probands and was less copious in blood from 18 maternal relatives (mean 81.3% {plus_minus} 8.5%). Single-muscle-fiber analysis showed significantly higher levels of mutant genomes in cytochrome c oxidase-negative fibers than in cytochrome c oxidase-positive fibers. The mutation was not found in >200 individuals, including normal controls and patients with other mitochondrial encephalomyopathies, thus fulfilling accepted criteria for pathogenicity. 23 refs., 3 figs., 1 tab.

  3. Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family

    PubMed Central

    Reiisi, Somayeh; Tabatabaiefar, Mohammad Amin; Sanati, Mohammad Hosein; Chaleshtori, Morteza Hashemzadeh

    2016-01-01

    Objective(s): Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive non-syndromic hearing loss (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide. Materials and Methods: The aim of the present study was to define the role and frequency of MYO15A gene mutation in Iranian families. In this study 30 Iranian families were enrolled with over three deaf children and negative for GJB2. Then linkage analysis was performed by six DFNB3 short tandem repeat markers. Following that, mutation detection accomplished using DNA sequencing. Results: One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A): as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls. Conclusion: Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein. PMID:27635202

  4. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  5. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  6. [Non-syndromic hereditary hearing impairment].

    PubMed

    Birkenhäger, R; Aschendorff, A; Schipper, J; Laszig, R

    2007-04-01

    Hearing impairment is the most common sensorineural disorder in humans. Approximately one of thousand new-borns is affected by severe to profound deafness at birth or during early childhood. Genetic causes account for around half of these cases of prelingual hearing impairment and the remainder are attributed to environmental factors. Genetic causes of hearing impairment in combination with a syndrome as Usher, Pendred are distinguished from non-syndromic hearing impairment. In the last years a tremendous growth in the localisation and identification of genes for non-syndromic hereditary hearing impairment has evolved. It has become clear that these conditions are genetically extremely heterogeneous. Approximately 120 different gene loci associated with non syndromic hearing impairment have been identified. Presently 54 gene loci associated with autosomal dominant mode of inheritance and 67 gene loci with autosomal recessive mode of inheritance have been identified; 7 are X-chromosome linked and 4 mitochondrial. Of these, 19 genes have been characterised for autosomal dominant (DFNA), 20 for autosomal recessive (DFNB), and 2 for X-linked (DFN) disorders. These genes encode proteins of diverse functions, including transcription factors, cytoskeletal and extracellular matrix components, and ion channels. Despite this heterogeneity, up to 50 % of prelingual recessive non-syndromic deafness can be attributed to mutations in the GJB2 gene (Connexin-26, gap-junction protein). However, the diversity of genes and genetic loci implicated in hearing loss illustrates the complexity of the genetic basis of hearing. Knowing the gene and the function of its products helps understanding the mechanisms of hearing.

  7. Hearing Impairment

    MedlinePlus

    ... may include inserting an object such as a cotton swab too far into the ear, a sudden explosion or other loud noise, a sudden change in air pressure, a head injury, or repeated ear infections. Sensorineural hearing impairment results from problems with or damage ...

  8. House Hearing

    NASA Image and Video Library

    2012-03-28

    Cristina Chaplain, director, Acquisition and Sourcing Management, U.S. Government Accountability Office testifies during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  9. House Hearing

    NASA Image and Video Library

    2012-03-28

    Retired astronaut Lt. Gen. Thomas Stafford, right, and Cristina Chaplain, director, Acquisition and Sourcing Management, U.S. Government Accountability Office listen during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  10. House Hearing

    NASA Image and Video Library

    2012-03-28

    Retired astronaut Lt. Gen. Thomas Stafford testifies during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  11. House Hearing

    NASA Image and Video Library

    2012-03-28

    William Gerstenmaier, Associate Administrator, Human Exploration and Operations Mission Directorate, NASA Headquarters, testifies during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  12. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    U.S. Senator Bill Nelson, D-Fla., and U.S. Senator Kay Bailey Hutchinson, R-Texas, confer during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  13. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    U.S. Senator Kay Bailey Hutchinson, R-Texas, questions NASA Administrator Charles Bolden during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    U.S. Senator Tom Udall, D-N.M., questions NASA Administrator Charles Bolden during a U.S. Senate Committee on Commerce, Science, and Transportation hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. House Hearing

    NASA Image and Video Library

    2012-03-28

    U.S. Congressman Steven Palazzo (R-MS) asks a question during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  16. House Hearing

    NASA Image and Video Library

    2012-03-28

    U.S. Congresswoman Eddie Bernice Johnson (D-TX) listens to testimony during a hearing before the House Committee on Science, Space, and Technology regarding access to and sustainability of the International Space Station, Wednesday, March 28, 2012 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Carla Cioffi)

  17. Senate Hearing

    NASA Image and Video Library

    2012-03-07

    View from the witness table in the Russell Senate Office Building prior to the start of a U.S. Senate Committee on Commerce, Science, and Transportation hearing with NASA Administrator Charles Bolden as the first witness on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  18. House Hearing

    NASA Image and Video Library

    2012-03-07

    Chairman of the U.S. House Science, Space and Technology Committee Rep. Ralph Hall, R-TX, asks a question of NASA Administrator Charles Bolden during a hearing on Wednesday, March 7, 2012 in Washington. Photo Credit: (NASA/Bill Ingalls)

  19. Whole Exome Sequencing Reveals Homozygous Mutations in RAI1, OTOF, and SLC26A4 Genes Associated with Nonsyndromic Hearing Loss in Altaian Families (South Siberia).

    PubMed

    Сhurbanov, Alexander Y; Karafet, Tatiana M; Morozov, Igor V; Mikhalskaia, Valeriia Yu; Zytsar, Marina V; Bondar, Alexander A; Posukh, Olga L

    2016-01-01

    Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies.

  20. Whole Exome Sequencing Reveals Homozygous Mutations in RAI1, OTOF, and SLC26A4 Genes Associated with Nonsyndromic Hearing Loss in Altaian Families (South Siberia)

    PubMed Central

    Karafet, Tatiana M.; Morozov, Igor V.; Mikhalskaia, Valeriia Yu.; Zytsar, Marina V.; Bondar, Alexander A.

    2016-01-01

    Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies. PMID:27082237

  1. Identification of functional tag single nucleotide polmorphisms within the entire CAT gene and their clinical relevance in patients with noise-induced hearing loss

    PubMed Central

    Yang, Junhui; Zhang, Jieyuan; Wang, Xiaoming; Wang, Chaoyong; Chen, Jichuan; Qian, Yu; Duan, Zhaoxia

    2015-01-01

    Objectives: Noise-induced hearing loss (NIHL) is an important occupational disease which results from an interaction between genetic and environmental factors. More and more evidences suggested that Catalase (CAT) gene polymorphism plays an important role in the development of NIHL. The aim of this study was to investigate the association of CAT gene polymorphisms with NIHL in a case-control study. Design: A total of 719 unrelated adult Chinese Han population, including 225 healthy volunteers and 494 noise-exposed workers were recruited in this study. Six tag single-nucleotide polymorphisms (tSNPs) were genotyped using an improved multiplex ligation detection reaction technique. Subsequently, the interaction between noise exposure level and genotypes and their effect on NIHL were analyzed using logistic regression. Results: Among six tSNPs, two of them (rs208679 and rs769217) were significantly associated with noise exposure level. For rs208679 recessive effect, GG genotype had a significantly increased of NIHL risk in the exposure level of < 85 dB; and for rs769217 dominant effect, the combined genotypes TT/TC had a significantly increased of NIHL risk in the exposure level of 85 dB~92 dB; and the haplotype A-G-T-C-A-C had a risk effect on the NIHL in the exposure level of 85 dB~92 dB. In addition, the rs769217 polymorphism could enhance the transcription activities of the CAT gene. Conclusions: This study identified CAT is a NIHL susceptibility gene when noise exposure levels are taken into account. Rs208679 and rs769217 polymorphisms might be used as relevant risk estimates for the development of NIHL in population with different noise exposure levels. PMID:26045794

  2. CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene.

    PubMed

    Heimer, Gali; Sadaka, Yair; Israelian, Lori; Feiglin, Ariel; Ruggieri, Alessandra; Marshall, Christian R; Scherer, Stephen W; Ganelin-Cohen, Esther; Marek-Yagel, Dina; Tzadok, Michal; Nissenkorn, Andreea; Anikster, Yair; Minassian, Berge A; Zeev, Bruria Ben

    2015-11-01

    We describe the molecular basis of a distinctive syndrome characterized by infantile stress-induced episodic weakness, ataxia, and sensorineural hearing loss, with permanent areflexia and optic nerve pallor. Whole exome sequencing identified a deleterious heterozygous c.2452 G>A, p.(E818K) variant in the ATP1A3 gene and structural analysis predicted its protein-destabilizing effect. This variant has not been reported in context with rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood, the 2 main diseases associated with ATP1A3. The clinical presentation in the family described here differs categorically from these diseases in age of onset, clinical course, cerebellar over extrapyramidal movement disorder predominance, and peripheral nervous system involvement. While this paper was in review, a highly resembling phenotype was reported in additional patients carrying the same c.2452 G>A variant. Our findings substantiate this variant as the cause of a unique inherited autosomal dominant neurologic syndrome that constitutes a third allelic disease of the ATP1A3 gene. © The Author(s) 2015.

  3. High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss.

    PubMed

    Alvarez, Araceli; del Castillo, Ignacio; Villamar, Manuela; Aguirre, Luis A; González-Neira, Anna; López-Nevot, Alicia; Moreno-Pelayo, Miguel A; Moreno, Felipe

    2005-09-01

    Molecular testing for mutations in the gene encoding connexin-26 (GJB2) at the DFNB1 locus has become the standard of care for genetic diagnosis and counseling of autosomal recessive non-syndromic hearing impairment (ARNSHI). The spectrum of mutations in GJB2 varies considerably among the populations, different alleles predominating in different ethnic groups. A cohort of 34 families of Spanish Romani (gypsies) with ARNSHI was screened for mutations in GJB2. We found that DFNB1 deafness accounts for 50% of all ARNSHI in Spanish gypsies. The predominating allele is W24X (79% of the DFNB1 alleles), and 35delG is the second most common allele (17%). An allele-specific PCR test was developed for the detection of the W24X mutation. By using this test, carrier frequencies were determined in two sample groups of gypsies from different Spanish regions (Andalusia and Catalonia), being 4% and 0%, respectively. Haplotype analysis for microsatellite markers closely flanking the GJB2 gene revealed five different haplotypes associated with the W24X mutation, all sharing the same allele from marker D13S141, suggesting that a founder effect for this mutation is responsible for its high prevalence among Spanish gypsies. (c) 2005 Wiley-Liss, Inc.

  4. Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss.

    PubMed

    Yu, Yong-qiang; Yang, Huai-an; Xiao, Ming; Wang, Jing-wei; Huang, Dong-yan; Bhambhani, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Jin, Yuan-zhe; Fu, Wei-neng; Zhang, Jie; Yu, Qian; Liang, Xue-ting; Zhang, Ming

    2015-09-01

    In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.

  5. [Association between CDH23 gene polymorphisms and susceptibility to noise-induced hearing loss in the Chinese population: a meta-analysis].

    PubMed

    Yu, J N; Wu, S S; He, C H; Zhang, C Y; Mu, H X; Ma, W S; Liu, B; Zhang, Y; Yu, S F

    2016-12-20

    Objective: To investigate the association between cadherin-23 (CDH23) gene polymorphisms and susceptibility to noise-induced hearing loss (NIHL) in the Chinese population through a meta-analysis. Methods: In June 2016, CNKI, VIP, Wanfang Data, and PubMed were searched for studies on the association between CDH23 gene polymorphisms and susceptibility to NIHL in the Chinese population. The articles were screened according to inclusion and exclusion criteria and related data were extracted. RevMan 5.3 was used for the meta-analysis. Results: A total of three Chinese articles were included. For CDH23-rs1227049, the risk of NIHL in people with C allele was 0.82 times (95%CI 0.39-1.73) that in people with G allele, the risk of NIHL in people with CG+CC genotype in the dominant model was 0.70 times (95%CI 0.34-1.43) that in people with GG genotype, the risk of NIHL in people with CC genotype in the recessive model was 1.23 times (95%CI 0.28-5.43) that in people with CG+GG genotype, and the risk of NIHL in people with CC genotype in the additive model was 1.05 times (95%CI 0.20-5.44) that in people with GG genotype (all P>0.05) . For CDH23-rs1227051, the risk of NIHL in people with T allele was 0.98 times (95%CI 0.71-1.37) that in people with C allele, and the risk of NIHL in people with CT+CC genotype in the dominant model was 1.09 times (95%CI 0.75-1.57) that in patients with TT genotype (both P>0.05) . Conclusion: There is still no enough evidence for the determination of CDH23-rs1227049 and CDH23-rs1227051 to be the susceptibility gene loci of NIHL.

  6. Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population

    PubMed Central

    Du, Jihong; Deng, Jianhua

    2016-01-01

    Background The aim of this study was to investigate whether the TGFA/TGFB3/MSX1 gene polymorphisms and haplotypes lead to individual differences between congenital non-syndromic hearing impairment (NSHI) patients and normal people in a Chinese population and to analyze the risk factors for NSHI. Material/Methods Between December 2010 and September 2014, 343 congenital NSHI patients were recruited as cases, and 272 healthy subjects were recruited as controls. Denaturing high-performance liquid chromatography (DHPLC) was used to identify genotypes, SHEsis software was used to conduct gene linkage disequilibrium and haplotype analyses, and regression analysis was performed to identify risk factors for congenital NSHI. Results The distribution of genotype frequencies and allele frequencies of TGFA rs3771494, TGFB3 rs3917201 and rs2268626, and MSX1 rs3821949 and rs62636562 were significantly different between the case and the control groups (all P<0.05). TGFA/TGFB3/MSX1 gene rs3771494, rs1058213, rs3917201, rs2268626, rs3821949, and rs62636562 haplotype analysis showed that haplotype CCGTAC and TTACGT might be protective factors (both P<0.001), while TTGCGC might be a risk factor for the normal population (P<0.001). The other risk factors include paternal smoking, advanced maternal age, maternal sickness history, maternal contact with pesticides or similar drugs, maternal abortion history, maternal medication history, maternal passive smoking history during pregnancy, rs3771494 CT, rs2268626 CC and TC, and rs3821949 GG and AG genotypes were risk factors (all P<0.05), while maternal vitamin supplements during pregnancy, rs3917201 GA, rs62636562 TT and CT genotypes were protective factors for congenital NSHI (all P<0.05). Conclusions rs3771494, rs3917201, rs2268626, rs3821949 and rs62636562 might be associated with congenital NSHI. PMID:27356075

  7. Genome-Wide Association Study Identifies Nox3 as a Critical Gene for Susceptibility to Noise-Induced Hearing Loss

    PubMed Central

    Lavinsky, Joel; Crow, Amanda L.; Pan, Calvin; Wang, Juemei; Aaron, Ksenia A.; Ho, Maria K.; Li, Qingzhong; Salehide, Pehzman; Myint, Anthony; Monges-Hernadez, Maya; Eskin, Eleazar; Allayee, Hooman; Lusis, Aldons J.; Friedman, Rick A.

    2015-01-01

    In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL. PMID:25880434

  8. Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss.

    PubMed

    Lavinsky, Joel; Crow, Amanda L; Pan, Calvin; Wang, Juemei; Aaron, Ksenia A; Ho, Maria K; Li, Qingzhong; Salehide, Pehzman; Myint, Anthony; Monges-Hernadez, Maya; Eskin, Eleazar; Allayee, Hooman; Lusis, Aldons J; Friedman, Rick A

    2015-04-01

    In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.

  9. Prospective mutation screening of three common deafness genes in a large Taiwanese Cohort with idiopathic bilateral sensorineural hearing impairment reveals a difference in the results between families from hospitals and those from rehabilitation facilities.

    PubMed

    Wu, Chen-Chi; Chen, Pei-Jer; Chiu, Yu-Hsun; Lu, Ying-Chang; Wu, Ming-Chueh; Hsu, Chuan-Jen

    2008-01-01

    Accurate epidemiological data on common deafness genes are essential to improve the efficiency and to reduce the cost of molecular diagnosis. They may depend on several factors, including a clear delineation of the source of patients being studied. In the present study, we hypothesize that patients with idiopathic sensorineural hearing loss recruited from different sources might reveal discrepancies in the epidemiological results of genetic screening, because patients from different sources might demonstrate distinct clinical or audiologic features and thus result in biased selection of subjects. To elucidate the relative importance of common deafness genes in Taiwanese and to verify our hypothesis, we conducted a prospective project screening mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with idiopathic bilateral sensorineural hearing loss, of which 325 families were recruited from hospitals and 95 from hearing rehabilitation facilities. Allele frequencies of common mutations in these three genes and distributions of the corresponding genotypes were then compared between the two groups. The allele frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele frequency of SLC26A4 mutations in the hospital group was significantly higher than that in the rehabilitation facility group (16.2 vs. 8.4%, chi(2)-test, p < 0.05), whereas no difference in the frequencies of GJB2 mutations and mitochondrial 12S rRNA mutations was found between the two groups. Distributions of probands classified by SLC26A4 genotypes were also different between the two groups (chi(2)-test, p < 0.05). Accordingly, a discrepancy in the genetic screening results might exist between different sources of idiopathic hearing-impaired patients. Further analysis of audiological results and construction of a logistic regression model showed that different

  10. Noise and Hearing Protection

    MedlinePlus

    ... most pharmacies. Will I hear other people and machine problems if I wear hearing protectors? Just as ... hear the noises that signify an improperly functioning machine. However, most workers readily adjust to the quieter ...

  11. Hearing Assistive Technology

    MedlinePlus

    ... Careers Certification Publications Events Advocacy Continuing Education Practice Management Research Home / Information for the Public / Hearing and Balance Hearing Assistive Technology Hearing Assistive Technology: FM Systems | Infrared Systems | Induction Loop Systems | One-to-One ...

  12. Hearing Problems in Children

    MedlinePlus

    Most children hear and listen from the moment they are born. They learn to talk by imitating the sounds around them ... United States are born deaf or hard-of-hearing. More lose their hearing later during childhood. Babies ...

  13. How to Get Hearing Aids

    MedlinePlus

    ... Consumer Products Hearing Aids How to get Hearing Aids Share Tweet Linkedin Pin it More sharing options ... my hearing aids? How do I get hearing aids? Before getting a hearing aid, you should consider ...

  14. Polymorphisms in genes involved in the free-radical process in patients with sudden sensorineural hearing loss and Ménière's disease.

    PubMed

    Teranishi, M; Uchida, Y; Nishio, N; Kato, K; Otake, H; Yoshida, T; Suzuki, H; Sone, M; Sugiura, S; Ando, F; Shimokata, H; Nakashima, T

    2013-07-01

    The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that free radicals are related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the association between genetic polymorphisms located in genes related to the free-radical process and susceptibility to SSNHL and Ménière's disease. We compared 83 patients affected by SSNHL and 83 patients affected by Ménière's disease with 2048 adults (for SSNHL) and 1946 adults (for Ménière's disease) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios (ORs) for SSNHL and Ménière's disease in individuals with polymorphisms in the genes: methionine synthase (MTR; rs1805087); methionine-synthase reductase (MTRR; rs1801394); nitric oxide synthase 3 (NOS3; rs1799983); caveolin 1 (Cav1; rs3840634); melatonin receptor 1B (MTNR1B; rs1387153); NAD(P)H oxidase p22(phox) subunit (NADH/NADPHp22phox; rs4673); and mitochondria 5178 (MT5178; rs28357984). The NOS3 polymorphism was significantly associated with a risk of SSNHL; in addition, the OR for the NOS3 polymorphism and SSNHL risk was 2.108 (CI, 1.343-3.309) with adjustment for age and sex. The Cav1 polymorphism was significantly associated with a risk of Ménière's disease; moreover, the OR for the Cav1 polymorphism and Ménière's disease risk was 1.849 (CI, 1.033-3.310) with adjustment for age and sex. In conclusion, the NOS3 and Cav1 polymorphisms were significantly associated with the risk of SSNHL and Ménière's disease, respectively.

  15. Co segregation of the m.1555A>G mutation in the MT-RNR1 gene and mutations in MT-ATP6 gene in a family with dilated mitochondrial cardiomyopathy and hearing loss: A whole mitochondrial genome screening.

    PubMed

    Alila-Fersi, Olfa; Chamkha, Imen; Majdoub, Imen; Gargouri, Lamia; Mkaouar-Rebai, Emna; Tabebi, Mouna; Tlili, Abdelaziz; Keskes, Leila; Mahfoudh, Abdelmajid; Fakhfakh, Faiza

    2017-02-26

    Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to dysfunction of the mitochondrial respiratory chain, which is responsible for the generation of most cellular energy. Because cardiac muscles are one of the high energy demanding tissues, mitochondrial cardiomyopathies is one of the most frequent mitochondria disorders. Mitochondrial cardiomyopathy has been associated with several point mutations of mtDNA in both genes encoded mitochondrial proteins and mitochondrial tRNA and rRNA. We reported here the first description of mutations in MT-ATP6 gene in two patients with clinical features of dilated mitochondrial cardiomyopathy. The mutational analysis of the whole mitochondrial DNA revealed the presence of m.1555A>G mutation in MT-RNR1 gene associated to the m.8527A>G (p.M>V) and the m.8392C>T (p.136P>S) variations in the mitochondrial MT-ATP6 gene in patient1 and his family members with variable phenotype including hearing impairment. The second patient with isolated mitochondrial cardiomyopathy presented the m.8605C>T (p.27P>S) mutation in the MT-ATP6 gene. The three mutations p.M1V, p.P27S and p.P136S detected in MT-ATP6 affected well conserved residues of the mitochondrial protein ATPase 6. In addition, the substitution of proline residue at position 27 and 136 effect hydrophobicity and structure flexibility conformation of the protein.

  16. Hearing Impairment in Congenitally Hypothyroid Patients

    PubMed Central

    Hashemipour, Mahin; Hovsepian, Silva; Hashemi, Mostafa; Amini, Massoud; Kelishadi, Roya; Sadeghi, Somaye

    2012-01-01

    Objective Thyroid hormone is necessary for normal development of the auditory system. The aim of this study was to investigate the rate of hearing impairment in congenitally hypothyroid (CH) patients, and its relation with factors such as CH severity and age at starting treatment, during CH screening program in Isfahan. Methods Hearing acuity was assessed in two groups of children with (94 patients aged 4 months – 3 years) and without CH (450), between 2000-2006. Otoacostic emission (OAE) was performed by a two step method. After two tests without OAE signals bilaterally, they were referred for auditory brainstem response (ABR) test. Subjects with both OAE and ABR abnormal test results were considered to have hearing problem. Obtained data was compared in case and control group and also CH patients with and without hearing impairment. Findings Three (3.2%) of patients and 1 of control group (0.2%) were diagnosed with sensorineural hearing loss. The rate of hearing loss was not different significantly in two studied groups (P>0.05). There was no difference between age of starting treatment and first T4 and TSH level in CH patients with and without hearing loss (P>0.05). CH neonates with hearing impairment had thyroid dyshormonogenesis according to the follow up results. Conclusion The rate of hearing loss was low among our studied CH patients. It may be due to proper management of CH patients. In view of the fact that all CH neonates were dyshormonogentic and considering the relation between certain gene mutations and hearing impairment in CH patients, further studies with larger sample size, with regard to different etiologies of CH should be investigated to indicate the possible gene mutations related to hearing loss in CH. PMID:23056865

  17. Hearing aids. I. Conventional hearing devices.

    PubMed

    Stach, B A; Gulya, A J

    1996-03-01

    State-of-the-art hearing aids incorporate advances in signal processing, miniaturization, and programmability. This technological progress has been accompanied by parallel enhancements in evaluating and fitting strategies. In addition, in the past several years, knowledge has increased about the influences of amplification on hearing ability and about the influences of hearing ability on benefit from amplification.

  18. Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study

    PubMed Central

    Li, Yanhong; Yu, Shanfa; Gu, Guizhen; Chen, Guoshun; Zheng, Yuxin; Jiao, Jie; Zhou, Wenhui; Wu, Hui; Zhang, Zengrui; Zhang, Huanling; He, Lihua; Yang, Qiuyue; Xu, Xiangrong

    2017-01-01

    Noise-induced hearing loss (NIHL) is the second-most frequent form of sensorineural hearing loss. When exposed to the same noise, some workers develop NIHL while others do not, suggesting that NIHL may be associated with genetic factors. To explore the relationship between single nucleotide polymorphisms (SNPs) in heat shock protein 70 (HSP70) genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility to NIHL in Han Chinese workers exposed to noise, a case-control association study was carried out with 286 hearing loss cases and 286 matched with gender, age, type of work, and exposure time, drawn from a population of 3790 noise-exposed workers. Four SNPs were selected and genotyped. Subsequently, the effects of the alleles and genotypes of the three HSP70 genes (HSPA1A, HSPA1B and HSPA1L) on NIHL were analyzed by using a conditional logistic regression. A generalized multiple dimensionality reduction (GMDR) was applied to further detect an interaction between the four SNPs. Compared with the combined genotypes CC/TC, carriers of the TT genotype of rs2763979 appeared to show greater susceptibility to NIHL (P = 0.042, adjusted OR = 1.731, 95% CI 1.021–2.935). A significant interaction between rs2763979 and CNE was found (P = 0.029), and a significant association was found between TT of s2763979 and NIHL (P = 0.024, adjusted OR = 5.694, 95%CI 1.256-25.817) in the 96 dB (A)≤CNE<101 dB (A) group. The results suggest that the rs2763979 locus of the HSP70 genes may be associated with susceptibility to NIHL in Chinese individuals, and other HSP70 genes may also be susceptibility genes for NIHL, but the results must be further replicated in additional independent sample sets. PMID:28182740

  19. Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

    PubMed

    Li, Yanhong; Yu, Shanfa; Gu, Guizhen; Chen, Guoshun; Zheng, Yuxin; Jiao, Jie; Zhou, Wenhui; Wu, Hui; Zhang, Zengrui; Zhang, Huanling; He, Lihua; Yang, Qiuyue; Xu, Xiangrong

    2017-01-01

    Noise-induced hearing loss (NIHL) is the second-most frequent form of sensorineural hearing loss. When exposed to the same noise, some workers develop NIHL while others do not, suggesting that NIHL may be associated with genetic factors. To explore the relationship between single nucleotide polymorphisms (SNPs) in heat shock protein 70 (HSP70) genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility to NIHL in Han Chinese workers exposed to noise, a case-control association study was carried out with 286 hearing loss cases and 286 matched with gender, age, type of work, and exposure time, drawn from a population of 3790 noise-exposed workers. Four SNPs were selected and genotyped. Subsequently, the effects of the alleles and genotypes of the three HSP70 genes (HSPA1A, HSPA1B and HSPA1L) on NIHL were analyzed by using a conditional logistic regression. A generalized multiple dimensionality reduction (GMDR) was applied to further detect an interaction between the four SNPs. Compared with the combined genotypes CC/TC, carriers of the TT genotype of rs2763979 appeared to show greater susceptibility to NIHL (P = 0.042, adjusted OR = 1.731, 95% CI 1.021-2.935). A significant interaction between rs2763979 and CNE was found (P = 0.029), and a significant association was found between TT of s2763979 and NIHL (P = 0.024, adjusted OR = 5.694, 95%CI 1.256-25.817) in the 96 dB (A)≤CNE<101 dB (A) group. The results suggest that the rs2763979 locus of the HSP70 genes may be associated with susceptibility to NIHL in Chinese individuals, and other HSP70 genes may also be susceptibility genes for NIHL, but the results must be further replicated in additional independent sample sets.

  20. Biophysical Mechanisms Underlying Hearing Loss Associated with a Shortened Tectorial Membrane

    NASA Astrophysics Data System (ADS)

    Oghalai, John S.; Xia, Anping; Liu, Christopher C.; Gao, Simon S.; Applegate, Brian E.; Puria, Sunil; Rousso, Itay; Steele, Charles

    2011-11-01

    The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Herein, we summarize key experimental data and modeling analyses that describe how biophysical alterations to these connections underlie hearing loss. The heterozygous C1509G mutation in alpha tectorin produces partial congenital hearing loss that progresses in humans. We engineered this mutation in mice, and histology revealed that the TM was shortened. DIC imaging of freshly-dissected cochlea as well as imaging with optical coherence tomography indicated that the TM is malformed and only stimulates the first row of OHCs. Noise exposure produced acute threshold shifts that fully recovered in Tecta+/+ mice although there was some OHC loss within all three rows at the cochlear base. In contrast, threshold shifts only partially recovered in TectaC1509G/+ mice. This was associated with OHC loss more apically and nearly entirely within the first row. Young's modulus of the TM, measured using atomic force microscopy, was substantially reduced at the middle and basal regions. Both the wild-type and heterozygous conditions were simulated in a computational model. This demonstrated that the normalized stress distribution levels between the TM and the tall cilia were significantly elevated in the middle region of the heterozygous cochlea. Another feature of the TectaC1509G/+ mutation is higher prestin expression within all three rows of OHCs. This increased electricallyevoked movements of the reticular lamina and otoacoustic emissions. Furthermore, electrical stimulation was associated with an increased risk of OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling of the TM from some OHCs not only leads to partial hearing loss, but also puts the OHCs that remain coupled at higher risk. Both the mechanics of the malformed TM and increased electromotility contribute to this higher risk profile.

  1. The Master Hearing Aid

    PubMed Central

    Curran, James R.

    2013-01-01

    As early as the 1930s the term Master Hearing Aid (MHA) described a device used in the fitting of hearing aids. In their original form, the MHA was a desktop system that allowed for simulated or actual adjustment of hearing aid components that resulted in a changed hearing aid response. Over the years the MHA saw many embodiments and contributed to a number of rationales for the fitting of hearing aids. During these same years, the MHA was viewed by many as an inappropriate means of demonstrating hearing aids; the audio quality of the desktop systems was often superior to the hearing aids themselves. These opinions and the evolution of the MHA have molded the modern perception of hearing aids and the techniques used in the fitting of hearing aids. This article reports on a history of the MHA and its influence on the fitting of hearing aids. PMID:23686682

  2. A Genetically-Encoded YFP Sensor with Enhanced Chloride Sensitivity, Photostability and Reduced pH Interference Demonstrates Augmented Transmembrane Chloride Movement by Gerbil Prestin (SLC26a5)

    PubMed Central

    Zhong, Sheng; Navaratnam, Dhasakumar; Santos-Sacchi, Joseph

    2014-01-01

    Background Chloride is the major anion in cells, with many diseases arising from disordered Cl− regulation. For the non-invasive investigation of Cl− flux, YFP-H148Q and its derivatives chameleon and Cl-Sensor previously were introduced as genetically encoded chloride indicators. Neither the Cl− sensitivity nor the pH-susceptibility of these modifications to YFP is optimal for precise measurements of Cl− under physiological conditions. Furthermore, the relatively poor photostability of YFP derivatives hinders their application for dynamic and quantitative Cl− measurements. Dynamic and accurate measurement of physiological concentrations of chloride would significantly affect our ability to study effects of chloride on cellular events. Methodology/Principal Findings In this study, we developed a series of YFP derivatives to remove pH interference, increase photostability and enhance chloride sensitivity. The final product, EYFP-F46L/Q69K/H148Q/I152L/V163S/S175G/S205V/A206K (monomeric Cl-YFP), has a chloride Kd of 14 mM and pKa of 5.9. The bleach time constant of 175 seconds is over 15-fold greater than wild-type EYFP. We have used the sensor fused to the transmembrane protein prestin (gerbil prestin, SLC26a5), and shown for the first time physiological (mM) chloride flux in HEK cells expressing this protein. This modified fluorescent protein will facilitate investigations of dynamics of chloride ions and their mediation of cell function. Conclusions Modifications to YFP (EYFP-F46L/Q69K/H148Q/I152L/V163S/S175G/S205V/A206K (monomeric Cl-YFP) results in a photostable fluorescent protein that allows measurement of physiological changes in chloride concentration while remaining minimally affected by changes in pH. PMID:24901231

  3. Canine hearing loss management.

    PubMed

    Scheifele, Lesa; Clark, John Greer; Scheifele, Peter M

    2012-11-01

    Dog owners and handlers are naturally concerned when suspicion of hearing loss arises for their dogs. Questions frequently asked of the veterinarian center on warning signs of canine hearing loss and what can be done for the dog if hearing loss is confirmed. This article addresses warning signs of canine hearing loss, communication training and safety awareness issues, and the feasibility of hearing aid amplification for dogs.

  4. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment

    PubMed Central

    Rendtorff, Nanna D.; Lodahl, Marianne; Boulahbel, Houda; Johansen, Ida R.; Pandya, Arti; Welch, Katherine O.; Norris, Virginia W.; Arnos, Kathleen S.; Bitner-Glindzicz, Maria; Emery, Sarah B.; Mets, Marilyn B.; Fagerheim, Toril; Eriksson, Kristina; Hansen, Lars; Bruhn, Helene; Möller, Claes; Lindholm, Sture; Ensgård, Stefan; Lesperance, Marci M.; Tranebjærg, Lisbeth

    2011-01-01

    Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene (OPA1), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1. Among these families, we found three heterozygous missense mutations in WFS1 segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the OPA1 p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1, p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1. Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome. PMID:21538838

  5. Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats

    PubMed Central

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Yang, Jun

    2016-01-01

    We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after

  6. Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Yang, Jun

    2016-07-28

    We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after

  7. Drug Induced Hearing Loss: Researchers Study Strategies to Preserve Hearing

    MedlinePlus

    ... JavaScript on. Feature: Drug-Induced Hearing Loss Researchers Study Strategies to Preserve Hearing Past Issues / Spring 2016 Table ... Read More "Drug Induced Hearing Loss" Articles Researchers Study Strategies to Preserve Hearing / What Is Ototoxicity? Spring 2016 ...

  8. [Hearing loss in adults].

    PubMed

    Eshraghi, Adrien A; Frachet, Bruno; Van De Water, Tom R; Eter, Elias

    2009-05-20

    The management of hearing loss in adults depends of etiology and its severity. It can be as simple as treating an external otitis, removing an impacted cerumen or a more complex one such as a surgery for otosclerosis. The hearing loss is managed mainly by new advances in hearing aids technology and implantable hearing devices which include BAHA, middle ear implant and cochlear implants. The research is focused on developing new molecules for intracochlear drug therapy to treat noise induced hearing loss, drug ototoxicity as well as hearing loss related to cochlear implant insertion trauma. Antioxidant molecules, molecules against apoptosis are at this time the most promising molecules than need further investigations.

  9. Effect of hearing aids on hearing.

    PubMed

    Podoshin, L; Kremer, M; Fradis, M; Feiglin, H

    1984-01-01

    We examined 114 patients aged 10 to 91 years with different kinds of hearing aids fitted in one ear only, the unaided ear acting as a control. They were re-examined several times during a period of follow-up from 1 to 9 years comparing the relative change in hearing due to hearing aid usage with various degrees of amplification of the aid. We compared the degree of hearing loss in the aided and unaided ear looking for evidence of a possible change in hearing related to the frequency of hearing aid usage in hours per day and in years, the maximum power output (MPO) and the gain of the aid. According to our findings there is no change in hearing between the aided and the unaided ear at the alpha = 0.05 probability level at least for 8 years. There is no effect of the long-term amplification of the hearing aid on deterioration of hearing comparing the aided ear and the unaided ear, but with high MPO of the aid, the patient should be followed up more frequently than with low MPO amplification.

  10. Mainstreaming the Hearing Impaired Student.

    ERIC Educational Resources Information Center

    Szelazkiewicz, Sara

    This review of the literature on mainstreaming students with hearing impairments begins by defining "hearing impairment,""deafness," and "hard of hearing". The paper briefly considers causes of hearing impairments and types of hearing impairments. Suggestions for preparing a class for a student with hearing loss includes having a visible class…

  11. Genetics of Hearing Loss

    MedlinePlus

    ... in Latin America Information For… Media Policy Makers Genetics of Hearing Loss Recommend on Facebook Tweet Share ... of hearing loss in babies is due to genetic causes. There are also a number of things ...

  12. Managing Hearing Loss

    MedlinePlus

    ... a total loss of hearing. It can be hereditary or it can result from disease, trauma, certain ... build-up, fluid, or a punctured eardrum. Medical treatment or surgery can usually restore conductive hearing loss. ...

  13. Hearing Aid Assembly

    NASA Technical Reports Server (NTRS)

    Grugel, Richard N. (Inventor)

    2002-01-01

    Progress in hearing aids has come a long way. Yet despite such progress hearing aids are not the perfect answer to many hearing problems. Some adult ears cannot accommodate tightly fitting hearing aids. Mouth movements such as chewing, talking, and athletic or other active endeavors also lead to loosely fitting ear molds. It is well accepted that loosely fitting hearing aids are the cause of feedback noise. Since feedback noise is the most common complaint of hearing aid wearers it has been the subject of various patents. Herein a hearing aid assembly is provided eliminating feedback noise. The assembly includes the combination of a hearing aid with a headset developed to constrict feedback noise.

  14. Evaluation of hearing impairment.

    PubMed

    Zadeh, M H; Selesnick, S H

    2001-01-01

    Hearing impairment is among the most common medical condition presenting to health care professionals. Ear anatomy, physiology, and pathology resulting in hearing loss are discussed. A systematic approach to evaluation, diagnosis, and treatment is presented.

  15. [The audiological analysis in the patients homozygous for the c.-23+1G>A mutation in the GJB2 gene presenting with the loss of hearing in Yakutiya].

    PubMed

    Teryutin, F M; Barashkov, N A; Kunel'skaya, N L; Pshennikova, V G; Solov'ev, A V

    2016-01-01

    In the course of previous investigations carried out in the Republic of Sakha (Yakutiya), we have identified the main molecular-genetic factor responsible for the hereditary impairment of hearing among the indigenous population (mostly the Yakuts).The disease was shown to be attributable to the c.-23+1G>A mutation localized in the splice donor site (exon 1) of the GJB2 (Cx26) gene. The present study involved the comprehensive audiological analysis of the patients homozygous for the c.-23+1G>A mutation in the GJB2 gene based on the results of the study of a large sample of the patients residing in Yakutiya. All individuals with the GJB2 genotype c.-23+1G>A/c.-23-1G>A (n=108) at the mean age of 14.32±4.7 years (all ethnic Yakuts)were examined with the use oftonal threshold audiometry for air conduction testing at the frequencies of 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and bone conduction testing at the frequencies of 0.25, 0.5, 1.0, and 4.0 with a step of 5.0 dB.The results of the ASSR test were used whenever tonal threshold audiometry proved impracticable The data obtained in the study characterize the allelic form of the disease associated with the GJB2 genotype c.-23+1G>A/c.-23-1G>A as the congenital bilateral symmetric (90.1%), sensorineural (90.1%) form of hearing impairment of variable severity (from grade 1 to complete deafness) with the «flat» audiological profile (median slope not more than 5.0 dB in the extended frequency range (EFR) of 0.5, 1.0, 2.0, and 4.0, kHz). It is concluded that the results of the audiological analysis performed in the present study give evidence of relatively homogeneous but variable in terms of severity impairment of hearing in the patients homozygous for the c.-23+1G>A mutation in the GJB2 (Cx26) gene. It may serve as a positive prognostic sign to be used in the development and prescription of hearing aids.

  16. Stem cells and molecular strategies to restore hearing

    PubMed Central

    PAULEY, S.; KOPECKY, B.; BEISEL, K.; SOUKUP, G.; FRITZSCH, B.

    2008-01-01

    Hearing loss is a costly and growing problem for the elderly population worldwide with millions of people being affected. There are currently two prosthetic devices available to minimize problems associated with the two forms of hearing loss: hearing aids that amplify sound to overcome middle ear based conductive hearing loss and cochlear implants that restore some hearing after neurosensory hearing loss. The current presentation provides information on the treatment of neurosensory hearing loss. Although the cochlear implant solution for neurosensory hearing loss is technologically advanced; it still provides only moderate hearing capacity in neurosensory deaf individuals. Inducible stem cells and molecular therapies are appealing alternatives to the cochlear implant and may provide more than a new form of treatment as they hold the promise for a cure. To this end, current insights into inducible stem cells that may provide cells for seeding the cochlea with the hope of new hair cell formation are being reviewed. Alternatively, similar to induction of stem cells, cells of the flat epithelium that remains after hair cell loss could be induced to proliferate and differentiate into hair cells. In either of these strategies, hair cell specific genes known to be essential for hair cell differentiation or maintenance such as ATOH1, POU4F3, GFI1, and miRNA-183 will be utilized with the hope of completely restoring hearing to all patients with hearing loss. PMID:18427387

  17. Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3).

    PubMed

    Stratakis, C A; Lin, J P; Rennert, O M

    1998-09-23

    It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis. Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA were present in 40 and 20%, respectively. Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%. In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome.

  18. Hearing-aid tester

    NASA Technical Reports Server (NTRS)

    Kessinger, R.; Polhemus, J. T.; Waring, J. G.

    1977-01-01

    Hearing aids are automatically checked by circuit that applies half-second test signal every thirty minutes. If hearing-aid output is distorted, too small, or if battery is too low, a warning lamp is activated. Test circuit is incorporated directly into hearing-aid package.

  19. Hearing Conservation Medical Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on hearing impairment is presented including causes and criteria for safe noise levels. The purpose of the Hearing Conservation Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Hearing Impairment at LeRC are discussed.

  20. Deafness and Hearing Loss.

    ERIC Educational Resources Information Center

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This brief overview provides information on the definition, incidence, and characteristics of children with hearing impairments and deafness. The federal definitions of hearing impairment and deafness are provided. The different types of hearing loss are noted, including: (1) conductive (caused by diseases or obstructions in the outer or middle…

  1. Rehabilitation of Hearing.

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Rehabilitation of hearing is considered in five conference papers. Two papers come from Poland: "Rehabilitation of Hearing in Children 'Deaf' in First 5 Years of Age" by D. Borkowska-Gaertig and others and "Possibilities of Hearing Improvement in Adults with Conservative Methods" by T. Bystrzanowska. Also included are…

  2. The LINC complex is essential for hearing

    PubMed Central

    Horn, Henning F.; Brownstein, Zippora; Lenz, Danielle R.; Shivatzki, Shaked; Dror, Amiel A.; Dagan-Rosenfeld, Orit; Friedman, Lilach M.; Roux, Kyle J.; Kozlov, Serguei; Jeang, Kuan-Teh; Frydman, Moshe; Burke, Brian; Stewart, Colin L.; Avraham, Karen B.

    2013-01-01

    Hereditary hearing loss is the most common sensory deficit. We determined that progressive high-frequency hearing loss in 2 families of Iraqi Jewish ancestry was due to homozygosity for the protein truncating mutation SYNE4 c.228delAT. SYNE4, a gene not previously associated with hearing loss, encodes nesprin-4 (NESP4), an outer nuclear membrane (ONM) protein expressed in the hair cells of the inner ear. The truncated NESP4 encoded by the families’ mutation did not localize to the ONM. NESP4 and SUN domain–containing protein 1 (SUN1), which localizes to the inner nuclear membrane (INM), are part of the linker of nucleoskeleton and cytoskeleton (LINC) complex in the nuclear envelope. Mice lacking either Nesp4 or Sun1 were evaluated for hair cell defects and hearing loss. In both Nesp4–/– and Sun1–/– mice, OHCs formed normally, but degenerated as hearing matured, leading to progressive hearing loss. The nuclei of OHCs from mutant mice failed to maintain their basal localization, potentially affecting cell motility and hence the response to sound. These results demonstrate that the LINC complex is essential for viability and normal morphology of OHCs and suggest that the position of the nucleus in sensory epithelial cells is critical for maintenance of normal hearing. PMID:23348741

  3. Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology.

    PubMed

    Sheppard, A; Hayes, S H; Chen, G-D; Ralli, M; Salvi, R

    2014-04-01

    Salicylate's ototoxic properties have been well established, inducing tinnitus and a sensory hearing loss when administered in high doses. Peripherally, acute dosing of salicylate causes frequency dependent reductions in DPOAEs and CAP amplitudes in low (<10 kHz) and high (>20 kHz) frequencies more than mid frequencies (10-20 kHz), which interestingly corresponds to the pitch of behaviourally-matched salicylate-induced tinnitus. Chronic salicylate dosing affects the peripheral system by causing a compensatory temporary enhancement in DPOAE amplitudes and up-regulation of prestin mRNA and protein expression. Despite salicylate's antioxidant properties, cultured cochlea studies indicate it also impairs spiral ganglion neurons (SGNs) by paradoxically causing an upsurge of superoxide radicals leading to apoptosis. Centrally, salicylate alters γ-aminobutyric acid (GABA) and serotonin mediated neurotransmission in the central nervous system (CNS), which results in classical and non-classical auditory regions showing hyperactivity after salicylate administration. In the auditory cortex (AC) and lateral amygdala (LA), neuron characteristic frequencies (CF) shift upward and downward to mid frequencies (10-20 kHz) altering tonotopy following salicylate administration. Additionally, current source density (CSD) analysis showed enhanced current flow into the supergranular layer of the auditory cortex after a high systemic dose of salicylate. In humans, auditory perception changes following salicylate or aspirin, including decreased word discrimination and temporal integration ability. The results of previous studies have partially identified the mechanisms that are involved in salicylate-induced tinnitus and hearing loss, however to date some interactions remain convoluted. This review discusses current knowledge of salicylate ototoxicity and interactions.

  4. Severe hearing loss in Dlxl mutant mice.

    PubMed

    Polley, Daniel B; Cobos, Inma; Merzenich, Michael M; Rubenstein, John L R

    2006-04-01

    The Dlx homeobox gene family participates in regulating middle and inner ear development. A significant role for Dlxl, in particular,has been demonstrated in the development of the middle ear ossicles, but the functional consequences of Dlx.l gene mutation on hearing thresholds has not been assessed. The present study characterizes auditory brainstem responses to click and tonal stimuli in a non-lethal variant of a Dlxl gene knockout. We found that peripheral hearing thresholds for click and tonal stimuli were significantly elevated in homozygous Dlxl knockout (Dlxl-/ ) compared to both heterozygous (Dlxl+/ ) and wild type (Dlxl+/+) mice. Thus, abnormal mor-phogenesis of the incus and stapes that has been documented previously with histological measures is now known to result in a severe peripheral hearing deficit.

  5. [Genotype--phenotype correlation limits in sensorineural hearing loss: case report of a three-year-old child with a bilateral cochleovestibular impairment and a molecular variant of the COCH gene].

    PubMed

    Montava, M; Roman, S; Sigaudy, S; Marlin, S; Nicollas, R; Triglia, J M

    2012-01-01

    Mutations of the COCH gene inherited in an autosomal dominant mode are responsible for late-onset cochleovestibular impairment on both sides. Our objective is to report the youngest patient (3 years) associating a molecular variant of the COCH gene and a cochleovestibular impairment on both sides. The clinical sequence has started with a vestibular dysfunction in a two-year-old child: recurrent rotatory dizziness during 12 months. At the age of 3, a sensorineural hearing loss on both sides has occured associated with spontaneous variation during 6 months. The lack of mutation of the connexin 26, connexin 30 and pendrin genes has reorientated the genetic investigation. A molecular variant of the COCH gene was found in the vWFA2 domain. It was an in-frame deletion predicting the synthesis of an abnormal protein in which 21 aminoacid were missing. Others family members with mutation were asymptomatics. In this isolated case report, the study was in favor of a non pathogenic molecular variant of the COCH gene. For all that, mutations of the COCH gene could be searched in progressive cochleovestibular dysfunctions on both sides in children, even without family affect.

  6. Hearing loss in space

    NASA Technical Reports Server (NTRS)

    Buckey, J. C. Jr; Musiek, F. E.; Kline-Schoder, R.; Clark, J. C.; Hart, S.; Havelka, J.

    2001-01-01

    BACKGROUND: Temporary and, in some cases, permanent hearing loss has been documented after long-duration spaceflights. METHODS: We examined all existing published data on hearing loss after space missions to characterize the losses. RESULTS: Data from Russian missions suggest that the hearing loss, when it occurs, affects mainly mid to high frequencies and that using hearing protection often might prevent the loss. Several significant questions remain about hearing loss in space. While the hearing loss has been presumed to be noise-induced, no clear link has been established between noise exposure and hearing loss during spaceflight. In one documented case of temporary hearing loss from the Shuttle-Mir program, the pattern of loss was atypical for a noise-induced loss. Continuous noise levels that have been measured on the Mir and previous space stations, while above engineering standards, are not at levels usually associated with hearing loss in ground-based studies (which have usually been limited to 8-10 h exposure periods). Attempts to measure hearing in space using threshold-based audiograms have been unsuccessful in both the American and Russian programs due to noise interference with the measurements. CONCLUSIONS: The existing data highlight the need for reliable monitoring of both hearing and noise in long-duration spaceflight.

  7. Hearing loss in space

    NASA Technical Reports Server (NTRS)

    Buckey, J. C. Jr; Musiek, F. E.; Kline-Schoder, R.; Clark, J. C.; Hart, S.; Havelka, J.

    2001-01-01

    BACKGROUND: Temporary and, in some cases, permanent hearing loss has been documented after long-duration spaceflights. METHODS: We examined all existing published data on hearing loss after space missions to characterize the losses. RESULTS: Data from Russian missions suggest that the hearing loss, when it occurs, affects mainly mid to high frequencies and that using hearing protection often might prevent the loss. Several significant questions remain about hearing loss in space. While the hearing loss has been presumed to be noise-induced, no clear link has been established between noise exposure and hearing loss during spaceflight. In one documented case of temporary hearing loss from the Shuttle-Mir program, the pattern of loss was atypical for a noise-induced loss. Continuous noise levels that have been measured on the Mir and previous space stations, while above engineering standards, are not at levels usually associated with hearing loss in ground-based studies (which have usually been limited to 8-10 h exposure periods). Attempts to measure hearing in space using threshold-based audiograms have been unsuccessful in both the American and Russian programs due to noise interference with the measurements. CONCLUSIONS: The existing data highlight the need for reliable monitoring of both hearing and noise in long-duration spaceflight.

  8. Research on Hearing and Balance--Current and Future Developments.

    ERIC Educational Resources Information Center

    Snow, James B., Jr.

    1997-01-01

    This article reviews current research that has located disease genes causing hearing impairments, discovered the ability of sensory cells of the inner ear to regenerate, developed vaccines to prevent otitis media, developed programmable hearing aids, improved cochlear implants, and demonstrated the positive effects of physical therapy with balance…

  9. Research on Hearing and Balance--Current and Future Developments.

    ERIC Educational Resources Information Center

    Snow, James B., Jr.

    1997-01-01

    This article reviews current research that has located disease genes causing hearing impairments, discovered the ability of sensory cells of the inner ear to regenerate, developed vaccines to prevent otitis media, developed programmable hearing aids, improved cochlear implants, and demonstrated the positive effects of physical therapy with balance…

  10. Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic)

    PubMed Central

    Posukh, Olga L.; Teryutin, Fedor M.; Solovyev, Aisen V.; Klarov, Leonid A.; Romanov, Georgii P.; Gotovtsev, Nyurgun N.; Kozhevnikov, Andrey A.; Kirillina, Elena V.; Sidorova, Oksana G.; Vasilyevа, Lena M.; Fedotova, Elvira E.; Morozov, Igor V.; Bondar, Alexander A.; Solovyevа, Natalya A.; Kononova, Sardana K.; Rafailov, Adyum M.; Sazonov, Nikolay N.; Alekseev, Anatoliy N.; Tomsky, Mikhail I.; Dzhemileva, Lilya U.; Khusnutdinova, Elza K.; Fedorova, Sardana A.

    2016-01-01

    Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic region in Russia. The complete sequencing of the non-coding and coding regions of the GJB2 gene was performed in 393 patients with HI (Yakuts—296, Russians—51, mixed and other ethnicities—46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n = 80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2 gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous state) were found in 192 out of 393 patients (48.85%). We found that the most frequent GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to be the most frequent among the Russian patients. The carrier frequencies of the c.-23+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and 2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical (2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic variants in HI in the population of the Sakha Republic (48.85%) was the highest among all of the previously studied regions of Asia. We suggest that extensive accumulation of the c.-23+1G>A pathogenic variant in the indigenous Yakut

  11. Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic).

    PubMed

    Barashkov, Nikolay A; Pshennikova, Vera G; Posukh, Olga L; Teryutin, Fedor M; Solovyev, Aisen V; Klarov, Leonid A; Romanov, Georgii P; Gotovtsev, Nyurgun N; Kozhevnikov, Andrey A; Kirillina, Elena V; Sidorova, Oksana G; Vasilyevа, Lena M; Fedotova, Elvira E; Morozov, Igor V; Bondar, Alexander A; Solovyevа, Natalya A; Kononova, Sardana K; Rafailov, Adyum M; Sazonov, Nikolay N; Alekseev, Anatoliy N; Tomsky, Mikhail I; Dzhemileva, Lilya U; Khusnutdinova, Elza K; Fedorova, Sardana A

    2016-01-01

    Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic region in Russia. The complete sequencing of the non-coding and coding regions of the GJB2 gene was performed in 393 patients with HI (Yakuts-296, Russians-51, mixed and other ethnicities-46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n = 80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2 gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous state) were found in 192 out of 393 patients (48.85%). We found that the most frequent GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to be the most frequent among the Russian patients. The carrier frequencies of the c.-23+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and 2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical (2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic variants in HI in the population of the Sakha Republic (48.85%) was the highest among all of the previously studied regions of Asia. We suggest that extensive accumulation of the c.-23+1G>A pathogenic variant in the indigenous Yakut

  12. Genetics of Nonsyndromic Congenital Hearing Loss

    PubMed Central

    Egilmez, Oguz Kadir; Kalcioglu, M. Tayyar

    2016-01-01

    Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear. PMID:26989561

  13. Congenital hearing loss.

    PubMed

    Korver, Anna M H; Smith, Richard J H; Van Camp, Guy; Schleiss, Mark R; Bitner-Glindzicz, Maria A K; Lustig, Lawrence R; Usami, Shin-Ichi; Boudewyns, An N

    2017-01-12

    Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

  14. Music and hearing aids.

    PubMed

    Madsen, Sara M K; Moore, Brian C J

    2014-10-31

    The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems. © The Author(s) 2014.

  15. Music and Hearing Aids

    PubMed Central

    Moore, Brian C. J.

    2014-01-01

    The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems. PMID:25361601

  16. Hearing: Noise-Induced Hearing Loss

    MedlinePlus

    ... a cochlear implant. A cochlear implant is an electronic hearing device that replaces the damaged inner ear ... by listening to parents, teachers, television, and radio. Music, the sounds of nature, and the voices of ...

  17. Use of Hearing Aids by Adults with Hearing Loss

    MedlinePlus

    ... Health Info » Statistics and Epidemiology Use of Hearing Aids by Adults with Hearing Loss [text version] Note: ... displays time trends in the use of hearing aids for adults (20–69 years) and older adults ( ...

  18. Do You Hear What Horton Hears?

    ERIC Educational Resources Information Center

    Snyder, Robert; Johnson, Jordan

    2010-01-01

    "I've never heard of a small speck of dust that is able to yell" says Horton of a sound he hears well (Geisel 1954). It is always valuable to connect science to student's interests and their everyday world--so what better way to teach concepts relating to sound than to read "Horton Hears a Who" by Dr. Seuss? Here the authors present several…

  19. [Sequencing analysis of whole SLC26A4 gene related to IVS7-2A > G mutation in 1552 moderate to profound sensorineural hearing loss patients in China].

    PubMed

    Yuan, Yong-yi; Dai, Pu; Zhu, Qing-wen; Kang, Dong-yang; Huang, De-liang

    2009-06-01

    To investigate the whole sequence of SLC26A4 gene among 1552 deaf students from 21 regions of China with SLC26A4 hot spot mutation IVS7-2A > G and analyze the epidemiological state of enlarged-vestibular-aqueduct-syndrome (EVAS) related hearing loss in China. DNA was extracted from peripheral blood of 1552 students from deaf and dumb school of 21 regions in China. The nationality of the 1552 cases covers Han (1290 cases), Uigur (69 cases), Hui (37 cases), Mongolia (31 cases), Yi, Zhuang, Bai, Miao and other 13 nationalities (125 cases). Firstly, all subjects were analyzed for the hot spot mutation IVS7-2A > G by direct sequencing. Those carrying a single heterozygous IVS7-2A > G were given further analyzed for the probable second mutation in other exons except exon7 and exon8 of SLC26A4. One hundred and fifty cases with normal hearing were in the control group. The sequencing results revealed 197 cases carrying IVS7-2A > G, of whom 83 carrying IVS7-2A > G homozygous mutation, 114 carrying IVS7-2A > G heterozygous mutation. Of the 114 cases with heterozygous IVS7-2A > G, 78 cases were found to have another mutation and 36 cases were found no other mutation in SLC26A4. Of the 1552 cases, the percentage of cases carrying homozygous IVS7-2A > G and compound heterozygous mutations was 10.37% (161/1552). Of the 78 cases with SLC26A4 compound heterozygous mutations, the mutations except IVS7-2A > G were found mainly in exon 19, 10, 17, 15, 11 + 12, 14 and 3. Twenty-one novel SLC26A4 mutations were found. In the control group, there were only 3 cases carrying heterozygous IVS7-2A > G, and no other mutation in SLC26A4 was found. SLC26A4 mutations account for at least 10% of EVAS related hereditary hearing loss in China. It's of great importance to screen SLC26A4 gene for making aetiological diagnosis for deafness. The discovery of novel variants of SLC26A4 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population. We also provide preliminary

  20. Hearing Lost, Hearing Gained. Hearing Aids Make a Difference. Tune in to Sound.

    ERIC Educational Resources Information Center

    Vandal, Ronda

    This illustrated booklet is intended to assist special education consultants, teachers, and parents to monitor hearing aid use by children with hearing impairments in the Northwest Territories (Canada). The first section presents basic information on what hearing aids are, types of personal hearing aids, and FM (frequency modulation) hearing aid…

  1. [Inner Ear Hearing Loss].

    PubMed

    Hesse, G

    2016-06-01

    Hearing loss is one of the most dominant handicaps in modern societies, which additionally very often is not realized or not admitted. About one quarter of the general population suffers from inner ear hearing loss and is therefore restricted in communicational skills. Demographic factors like increasing age play an important role as well as environmental influences and an increasing sound and noise exposure especially in leisure activities. Thus borders between a "classical" presbyacusis - if it ever existed - and envirionmentally induced hearing loss disappear. Today restrictions in hearing ability develop earlier in age but at the same time they are detected and diagnosed earlier. This paper can eventually enlighten the wide field of inner ear hearing loss only fragmentarily; therefore mainly new research, findings and developments are reviewed. The first part discusses new aspects of diagnostics of inner ear hearing loss and different etiologies.

  2. Hereditary hearing loss: from human mutation to mechanism.

    PubMed

    Lenz, Danielle R; Avraham, Karen B

    2011-11-01

    The genetic heterogeneity of hereditary hearing loss is thus far represented by hundreds of genes encoding a large variety of proteins. Mutations in these genes have been discovered for patients with different modes of inheritance and types of hearing loss, ranging from syndromic to non-syndromic and mild to profound. In many cases, the mechanisms whereby the mutations lead to hearing loss have been partly elucidated using cell culture systems and mouse and other animal models. The discovery of the genes has completely changed the practice of genetic counseling in this area, providing potential diagnosis in many cases that can be coupled with clinical phenotypes and offer predictive information for families. In this review we provide three examples of gene discovery in families with hereditary hearing loss, all associated with elucidation of some of the mechanisms leading to hair cell degeneration and pathology of deafness.

  3. Hearing or speech impairment - resources

    MedlinePlus

    Resources - hearing or speech impairment ... The following organizations are good resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell. ...

  4. Hearing and Speech at Seven

    ERIC Educational Resources Information Center

    Sheridan, Mary D.; Peckham, Catherine S.

    1973-01-01

    Evaluated for social and educational aspects at 7 years of age were 133 children with moderate hearing loss, 46 children with severe unilateral hearing loss, and 215 children with normal hearing but with unintelligible speech. (DB)

  5. Screening Newborns' Hearing Now Standard

    MedlinePlus

    ... Javascript on. Feature: Taste, Smell, Hearing, Language, Voice, Balance Screening Newborns' Hearing Now Standard Past Issues / Fall ... gov . Read More "Taste, Smell, Hearing, Language, Voice, Balance" Articles At Last: A National Test of Taste ...

  6. Hearing Conservation Live #2430

    SciTech Connect

    Chochoms, Michael

    2016-08-09

    Occupational hearing loss is one of the most common work-related illnesses in the United States (US). From 22 to 30 million US workers are exposed to hazardous noise levels at work, and 25% of these workers will develop permanent hearing loss. Hearing loss from noise is slow and painless, and you can have a disability before you notice it. This course presents the hazards associated with workplace noise, the purpose and elements of the Los Alamos National Laboratory (LANL) Hearing Conservation Program (HCP), and controls that are available to reduce your exposure to hazardous levels of noise.

  7. Hearing protection for miners

    SciTech Connect

    Schulz, T.

    2008-10-15

    A NIOSH analysis showed that at age 50 approximately 90% of coal miners have a hearing impairment, yet noise included hearing loss is 100% preventable. The article discusses requirements of the MSHA regulations, 30 CFR Part 62 - occupational noise exposure (2000) and a 2008-MSHA document describing technologically achievable and promising controls for several types of mining machinery. Hearing protection is still required for exposure to greater than 90 dBA. These are now commercially available ways to determine how much attenuation an individual gets from a given hearing protector, known as 'fit testing'. 3 refs., 1 fig., 1 tab., 1 photo.

  8. Underwater hearing: A review

    NASA Astrophysics Data System (ADS)

    Al-Masri, M.; Martin, A.; Nedwell, J.

    1993-05-01

    In view of the prevalence of hearing loss among commercial divers and the absence of widely accepted noise exposure limits for occupational underwater use, a review of studies of underwater hearing thresholds and hearing mechanisms was undertaken with the ultimate aim of developing noise exposure limits. Previous studies of underwater hearing thresholds appear to show that the ear underwater is less sensitive than compared with air. However, a surprisingly wide range of values for underwater hearing thresholds was reported, for example 35-90 dB SPL(re 20 MuPa) at 0.25 kHz and 30-80 dB at 1 kHz. No representative single threshold curve can be extracted with any validity. Possible reasons for such a wide scatter of results include high underwater ambient noise levels which may have masked the subjects underwater hearing thresholds, ill defined stimuli and underwater sound fields, and variable and informal audiometric methodology. Previous authors have proposed three somewhat interlinked theories to explain how sound is transmitted from water to the cochlea. These involve: the 'auricular' conduction pathway, the bone conduction pathway, and the dual conduction pathway. Up to this day, no one pathway has been shown to predominate, and all of them have been poorly evaluated. It is also possible that the presence of air bubbles in the ear canal and increased water depth may have significant effects on underwater hearing thresholds. These effects may be dependent on the underwater hearing mechanism. Again, the studies reviewed give conflicting results and no valid conclusion can be drawn. It is apparent that further experimental studies are required to establish underwater hearing thresholds and to provide an understanding of the mechanisms of hearing underwater. These should be based upon suitable facilities and methodologies for testing hearing thresholds underwater following modern and scientific audio metric practice.

  9. Molecular (SNP) Analyses of Overlapping Hemizygous Deletions of 10q25.3 to 10qter in Four Patients: Evidence for HMX2 and HMX3 as Candidate Genes in Hearing and Vestibular Function

    PubMed Central

    Miller, Nathaniel D.; Nance, Melonie A.; Wohler, Elizabeth S.; Hoover-Fong, Julie E.; Lisi, Emily; Thomas, George H.; Pevsner, Jonathan

    2009-01-01

    We report on the analyses of four unrelated patients with de novo, overlapping, hemizygous deletions of the long arm of chromosome 10. These include two small terminal deletions (10q26.2 to 10qter), a larger terminal deletion (10q26.12 to 10qter), and an interstitial deletion (10q25.3q26.13). Single nucleotide polymorphism (SNP) studies (Illumina 550 K) established that these deletions resulted in the hemizygous loss of ∼6.1, ∼6.1, ∼12.5, and ∼7.0 Mb respectively. Additionally, these data establish that Patients 1, 2, and 3 share common, distal, hemizygous deleted regions of 6.09 Mb containing 37 RefSeq genes. Patients 3 and 4 share a 2.52 Mb deleted region corresponding to the proximal deleted region of Patient 3 and the distal deleted region of Patient 4. This common, hemizygous region contains 20 RefSeq genes including two H6 family homeobox genes (HMX2 and HMX3). Based on previous reports that Hmx2/Hmx3 knockout mice have vestibular anomalies, we propose that hemizygous deletions of HMX2 and HMX3 are responsible for the inner ear malformations observed from CT images, vestibular dysfunction, and congenital sensorineural hearing loss found in Patients 3 and 4. PMID:19253379

  10. Genetics of Hearing and Deafness

    PubMed Central

    ANGELI, SIMON; LIN, XI; LIU, XUE ZHONG

    2015-01-01

    This article is a review of the genes and genetic disorders that affect hearing in humans and a few selected mouse models of deafness. Genetics is playing an increasingly critical role in the practice of medicine. This is not only in part to the importance that genetic knowledge has on traditional genetic diseases but also in part to the fact that genetic knowledge provides an understanding of the fundamental biological process of most diseases. The proteins coded by the genes related to hearing loss (HL) are involved in many functions in the ear, such as cochlear fluid homeostasis, ionic channels, stereocilia morphology and function, synaptic transmission, gene regulation, and others. Mouse models play a crucial role in understanding of the pathogenesis associated with these genes. Different types of familial HL have been recognized for years; however, in the last two decades, there has been tremendous progress in the discovery of gene mutations that cause deafness. Most of the cases of genetic deafness recognized today are monogenic disorders that can be broadly classified by the mode of inheritance (i.e., autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance) and by the presence of associated phenotypic features (i.e., syndromic; and nonsyndromic). In terms of nonsyndromic HL, the chromosomal locations are currently known for ~ 125 loci (54 for dominant and 71 for recessive deafness), 64 genes have been identified (24 for dominant and 40 for recessive deafness), and there are many more loci for syndromic deafness and X-linked and mitochondrial DNA disorders (http://hereditaryhearingloss.org). Thus, today’s clinician must understand the science of medical genetics as this knowledge can lead to more effective disease diagnosis, counseling, treatment, and prevention. PMID:23044516

  11. Genetics of hearing and deafness.

    PubMed

    Angeli, Simon; Lin, Xi; Liu, Xue Zhong

    2012-11-01

    This article is a review of the genes and genetic disorders that affect hearing in humans and a few selected mouse models of deafness. Genetics is playing an increasingly critical role in the practice of medicine. This is not only in part to the importance that genetic knowledge has on traditional genetic diseases but also in part to the fact that genetic knowledge provides an understanding of the fundamental biological process of most diseases. The proteins coded by the genes related to hearing loss (HL) are involved in many functions in the ear, such as cochlear fluid homeostasis, ionic channels, stereocilia morphology and function, synaptic transmission, gene regulation, and others. Mouse models play a crucial role in understanding of the pathogenesis associated with these genes. Different types of familial HL have been recognized for years; however, in the last two decades, there has been tremendous progress in the discovery of gene mutations that cause deafness. Most of the cases of genetic deafness recognized today are monogenic disorders that can be broadly classified by the mode of inheritance (i.e., autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance) and by the presence of associated phenotypic features (i.e., syndromic; and nonsyndromic). In terms of nonsyndromic HL, the chromosomal locations are currently known for ∼ 125 loci (54 for dominant and 71 for recessive deafness), 64 genes have been identified (24 for dominant and 40 for recessive deafness), and there are many more loci for syndromic deafness and X-linked and mitochondrial DNA disorders (http://hereditaryhearingloss.org). Thus, today's clinician must understand the science of medical genetics as this knowledge can lead to more effective disease diagnosis, counseling, treatment, and prevention.

  12. Hearing Loss and Cytomegalovirus.

    ERIC Educational Resources Information Center

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  13. Hearing Loss and Cytomegalovirus.

    ERIC Educational Resources Information Center

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  14. Hearing Disorders and Deafness

    MedlinePlus

    ... be helped. Deafness can keep you from hearing sound at all. What causes hearing loss? Some possibilities are Heredity Diseases such ... is usually permanent. The other kind happens when sound waves cannot reach your ... eardrum can cause it. Treatment or surgery can often reverse this ...

  15. Hearing loss and music

    MedlinePlus

    ... repeated exposure to loud noise and music can cause hearing loss. Decibels of Sound and Hearing Loss The decibel (dB) is a ... can make you unaware of the pain louder sounds can cause. Rest your ears for 24 hours after exposure ...

  16. [Hearing disorders in aphasia].

    PubMed

    Läßig, A K; Kreter, S; Nospes, S; Keilmann, A

    2013-08-01

    Aphasia is an acquired communication disorder that often involves receptive language abilities. After clinical assessment it is often not clear if this is partially due to a hearing loss, which can be compensated by hearing aids facilitating the rehabilitative process.In the present study the hearing ability of 88 male and female patients with aphasia after stroke, all of whom suffered from a left-hemispheric ischemia was assessed in the rehabilitative setting.We found that a majority of patients (72, 82%) was able to perform pure tone audiometry. 15 aphasic patients (21%) showed a hearing loss and were not fitted with hearing aids.Patients with aphasia are due to their central speech disorders in their communication skills limited, so that the therapeutic success is further reduced by an existing hearing loss. Due to the demographic development of our people and with the age increasing prevalence of hearing impairment hearing screening in the post-acute phase in aphasic patients is justified by pure tone audiometry. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Diagnosis of Hearing Loss.

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Seven conference papers from the U.S.S.R., India, Poland, Czechoslovakia, and Yugoslavia consider the diagnosis of hearing loss. They are "Examination of Hearing of Children, Aged from 2 to 5, by Means of Playing Audiometry" by A. P. Kossacheva, "A Study of the Etiology and Pattern of Deafness in a School for the Deaf in Madras,…

  18. The Hearing Environment

    ERIC Educational Resources Information Center

    Capewell, Carmel

    2014-01-01

    Glue ear, a condition resulting in intermittent hearing loss in young children, affects about 80% of young children under seven years old. About 60% of children will spend a third of their time unable to hear within normal thresholds. Teachers are unlikely to consider the sound quality in classrooms. In my research young people provided…

  19. The Hearing Environment

    ERIC Educational Resources Information Center

    Capewell, Carmel

    2014-01-01

    Glue ear, a condition resulting in intermittent hearing loss in young children, affects about 80% of young children under seven years old. About 60% of children will spend a third of their time unable to hear within normal thresholds. Teachers are unlikely to consider the sound quality in classrooms. In my research young people provided…

  20. Hearing impairment in Stickler syndrome: a systematic review

    PubMed Central

    2012-01-01

    Background Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial and auditory defects. It is caused by mutations in different collagen genes, namely COL2A1, COL11A1 and COL11A2 (autosomal dominant inheritance), and COL9A1 and COL9A2 (autosomal recessive inheritance). The auditory phenotype in Stickler syndrome is inconsistently reported. Therefore we performed a systematic review of the literature to give an up-to-date overview of hearing loss in Stickler syndrome, and correlated it with the genotype. Methods English-language literature was reviewed through searches of PubMed and Web of Science, in order to find relevant articles describing auditory features in Stickler patients, along with genotype. Prevalences of hearing loss are calculated and correlated with the different affected genes and type of mutation. Results 313 patients (102 families) individually described in 46 articles were included. Hearing loss was found in 62.9%, mostly mild to moderate when reported. Hearing impairment was predominantly sensorineural (67.8%). Conductive (14.1%) and mixed (18.1%) hearing loss was primarily found in young patients or patients with a palatal defect. Overall, mutations in COL11A1 (82.5%) and COL11A2 (94.1%) seem to be more frequently associated with hearing impairment than mutations in COL2A1 (52.2%). Conclusions Hearing impairment in patients with Stickler syndrome is common. Sensorineural hearing loss predominates, but also conductive hearing loss, especially in children and patients with a palatal defect, may occur. The distinct disease-causing collagen genes are associated with a different prevalence of hearing impairment, but still large phenotypic variation exists. Regular auditory follow-up is strongly advised, particularly because many Stickler patients are visually impaired. PMID:23110709

  1. Hearing Aid Tester

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Hearing aids often develop malfunctions that are not detected by the wearer. This is particularly true when the wearers are school-age children. Studies of selected groups showed that from 30 to more than 50 percent of school children were not getting adequate benefit from their hearing aids because of unrecognized malfunctions, usually low or dead batteries. This can be serious because hearing impairment retards a child's educational progress. NASA technology incorporated in the Hearing Aid Malfunction Detection Unit (HAMDU), the device pictured, is expected to provide an effective countermeasure to the childrens' hearing aid problem. A patent license has been awarded to a minority-owned firm, Hopkins International Company, a subsidiary of H. H. Aerospace Design Co., Inc., Elmford, New York. The company plans early commercial availability of its version of the device.

  2. Individual Hearing Loss

    PubMed Central

    Dau, Torsten; Christensen-Dalsgaard, Jakob; Tranebjærg, Lisbeth; Andersen, Ture; Poulsen, Torben

    2016-01-01

    It is well-established that hearing loss does not only lead to a reduction of hearing sensitivity. Large individual differences are typically observed among listeners with hearing impairment in a wide range of suprathreshold auditory measures. In many cases, audiometric thresholds cannot fully account for such individual differences, which make it challenging to find adequate compensation strategies in hearing devices. How to characterize, model, and compensate for individual hearing loss were the main topics of the fifth International Symposium on Auditory and Audiological Research (ISAAR), held in Nyborg, Denmark, in August 2015. The following collection of papers results from some of the work that was presented and discussed at the symposium. PMID:27566802

  3. [Fully implantable hearing systems].

    PubMed

    Maurer, J

    2009-03-01

    As yet comparatively little experience has been gained with fully implantable hearing systems, as the two systems available at present have only recently received CE permission for Europe and the FDA permissions are still pending in the USA. Additionally the technology is expensive and usually not covered by insurance companies. However, it could be shown that by careful patient selection and very careful surgical techniques, good results can be achieved with this highly sensitive technology, often with better patient satisfaction and hearing quality than with conventional hearing aids. To spread the technology further, the systems must also show reliable results on a broad application. Further surgery to change the batteries should not be necessary more frequently than with cardiac pacemakers. Not all technical problems are finally solved. However, it is to be foreseen that fully implantable hearing systems will be a good long-term alternative to conventional hearing aids for some patients.

  4. Sudden Sensorineural Hearing Loss

    PubMed Central

    Kuhn, Maggie; Heman-Ackah, Selena E.; Shaikh, Jamil A.

    2011-01-01

    Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram. PMID:21606048

  5. Hearing in Insects.

    PubMed

    Göpfert, Martin C; Hennig, R Matthias

    2016-01-01

    Insect hearing has independently evolved multiple times in the context of intraspecific communication and predator detection by transforming proprioceptive organs into ears. Research over the past decade, ranging from the biophysics of sound reception to molecular aspects of auditory transduction to the neuronal mechanisms of auditory signal processing, has greatly advanced our understanding of how insects hear. Apart from evolutionary innovations that seem unique to insect hearing, parallels between insect and vertebrate auditory systems have been uncovered, and the auditory sensory cells of insects and vertebrates turned out to be evolutionarily related. This review summarizes our current understanding of insect hearing. It also discusses recent advances in insect auditory research, which have put forward insect auditory systems for studying biological aspects that extend beyond hearing, such as cilium function, neuronal signal computation, and sensory system evolution.

  6. Studies of normal hearing.

    PubMed

    Catlin, F I

    1984-01-01

    Auditory function changes continually from birth to old age. A variety of methods to assess hearing have evolved since the invention of the audiometer. Types of measurement include: electrical response in the central nervous system, cochlear acuity and speech responses. While some of these tests correlate fairly well with each other, their ability to represent overall hearing function is questionable. Other attempts to improve the assessment of hearing have been made in the area of self-appraisal, but these, too, have significant limitations. Most self-report and peer appraisal questionnaires have been established by studies of hearing-impaired populations. Norms for these techniques in normal-hearing populations need to be established. There is still room for valid tests of everyday communication. What we have in measurement procedures does not achieve this goal. Research studies of today will hopefully produce better definition of normal auditory function.

  7. Hearing and dementia.

    PubMed

    Hardy, Chris J D; Marshall, Charles R; Golden, Hannah L; Clark, Camilla N; Mummery, Catherine J; Griffiths, Timothy D; Bamiou, Doris-Eva; Warren, Jason D

    2016-11-01

    Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia.

  8. Hearing Aids and Hearing Impaired Students in Rural Schools.

    ERIC Educational Resources Information Center

    Woodford, Charles

    This paper describes functions of the components of hearing aids and provides a detailed procedure to detect hearing aid dysfunctions. The most common type of hearing aids for school children are the behind the ear type. Various hearing aid components change sound into an electrical signal, which is amplified and adjusted by a volume control. The…

  9. 49 CFR 1113.1 - Scheduling hearings; continued hearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Scheduling hearings; continued hearings. 1113.1 Section 1113.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE ORAL HEARING § 1113.1 Scheduling hearings...

  10. Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran.

    PubMed

    Laleh, Masoud Akbarzadeh; Naseri, Marzieh; Zonouzi, Ali Akbar Poursadegh; Zonouzi, Ahmad Poursadegh; Masoudi, Marjan; Ahangari, Najmeh; Shams, Leila; Nejatizadeh, Azim

    2017-01-01

    We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran.

  11. Restoration of hearing by hearing aids: conventional hearing aids – implantable hearing aids – cochlear implants – auditory brainstem implants

    PubMed Central

    Leuwer, R.; Müller, J.

    2005-01-01

    Aim of this report is to explain the current concept of hearing restoration using hearing aids. At present the main issues of conventional hearing aids are the relative benefits of analogue versus digital devices and different strategies for the improvement of hearing in noise. Implantable hearing aids provide a better sound quality and less distortion. The lack of directional microphones is the major disadvantage of the partially implantable hearing aids commercially available. Two different clinical studies about fully implantable hearing aids have been started in 2004. One of the most-promising developments seems to be the electric-acoustic stimulation. PMID:22073051

  12. Hearing in Cavefishes.

    PubMed

    Soares, Daphne; Niemiller, Matthew L; Higgs, Dennis M

    2016-01-01

    Caves and associated subterranean habitats represent some of the harshest environments on Earth, yet many organisms, including fishes, have colonized and thrive in these habitats despite the complete absence of light, and other abiotic and biotic constraints. Over 170 species of fishes are considered obligate subterranean inhabitants (stygobionts) that exhibit some degree of troglomorphy, including degeneration of eyes and reduction in pigmentation. To compensate for lack of vision, many species have evolved constructive changes to non-visual sensory modalities. In this chapter we review hearing in cavefishes, with particular emphasize on our own studies on amblyopsid cavefishes. Hearing in cavefishes has not been well studied to date, as hearing ability has only been examined in four species. Two species show no differences in hearing ability relative to their surface relatives, while the other two species (family Amblyopsidae) exhibit regression in the form of reduced hearing range and reduction in hair cell densities on sensory epithelia. In addition to reviewing our current knowledge on cavefish hearing, we offer suggestions for future avenues of research on cavefish hearing and discuss the influence of Popper and Fay on the field of cavefish bioacoustics.

  13. Novel PTPRQ mutations identified in three congenital hearing loss patients with various types of hearing loss

    PubMed Central

    Sakuma, Naoko; Moteki, Hideaki; Azaiez, Hela; Booth, Kevin T; Takahashi, Masahiro; Arai, Yasuhiro; Shearer, A Eliot; Sloan, Christina M; Nishio, Shin-ya; Kolbe, Diana L; Iwasaki, Satoshi; Oridate, Nobuhiko; Smith, Richard J H; Usami, Shin-ichi

    2015-01-01

    Objective We present three patients with congenital sensorineural hearing loss (SNHL) caused by the novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods Two hundred and twenty (220) Japanese subjects with sensorineural hearing loss from unrelated and non-consanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel sequencing of all known non-syndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results Four novel causative PTPRQ mutations were identified in three cases. Case 1 had progressive profound SNHL with homozygous nonsense mutation. Case 2 had non-progressive profound SNHL with compound heterozygous mutation (nonsense and missense mutation). Case 3 had non-progressive moderate SNHL with compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlation between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutation appeared to be responsible for the vestibular dysfunction. PMID:25788564

  14. Accessibility for the hearing impaired.

    PubMed

    Alberti, P W

    1999-10-05

    The social anthropology of mild hearing loss is gradually being accepted, as it affects both children and adults. With this comes the understanding that effective aural communication requires adequate sound sources and a good transmission medium as well as good hearing. If the first two conditions are met, much hearing disability might be avoided without resorting to a hearing aid. A plea is made for better accessibility for the hearing impaired by improving environmental conditions for acoustic signals, especially speech.

  15. Keys to Effective Hearing Conservation Programs: Hearing Status of School-Age Children.

    ERIC Educational Resources Information Center

    Anderson, Karen L.

    This paper addresses incidence of hearing loss in school-age children, components of hearing conservation programs, and hearing loss education. Incidence figures for the following hearing loss categories are detailed: unilateral hearing loss, fluctuating hearing loss, minimal sensorineural hearing loss, and mild to profound hearing loss.…

  16. Micromechanics of hearing

    NASA Astrophysics Data System (ADS)

    Hudspeth, A. J.

    2015-12-01

    The following summarizes the key points addressed during a tutorial session on the Micromechanics of Hearing that took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. The tutorial was intended to present an overview of basic ideas and to address topics of current interest relevant to the Workshop. The session was recorded, and the audio file and accompanying visual content of the presentation can be found in the Mechanics of Hearing Digital Library (www.mechanicsofhearing.org).

  17. Screening of Connexin 26 in Nonsyndromic Hearing Loss

    PubMed Central

    Moreira, Danielle; Silva, Daniela da; Lopez, Priscila; Mantovani, Jair Cortez

    2014-01-01

    Introduction The first locus for nonsyndromic autosomal recessive hearing loss is on chromosome 13q11–22. The 35delG mutation is present in 80% of cases in which GJB2 is involved, which makes the study of this mutation very important. The viability and benefits of screening for mutations in the connexin 26 gene are now beginning to change the diagnostic evaluation and identification of the etiology of hearing loss. Objective To investigate the occurrence of the 35delG mutation in patients with nonsyndromic sensorineural hearing loss and their first degree relatives. Methods This transversal study included 72 patients from the local hospital. The patients were divided into three groups: group A, sensorineural hearing loss (n = 58); group B, first-degree relatives of group A with sensorineural hearing loss (n = 09); and group C, first-degree relatives of patients from group A without hearing loss (n = 05). All patients had audiological evaluation and genetic testing of the 35delG mutation. Results The 35delG mutation was found in four heterozygous mutations (three of them found in the same family). The other heterozygous mutation was found in a female patient with bilateral, moderate, prelingual, sensorineural hearing loss. A single homozygous mutation was found in a male patient, with severe sensorineural hearing loss in his right ear and profound hearing loss in the left ear. Conclusions The 35delG mutation was found in 7% of the cases. The test is easy to perform and inexpensive, but it is necessary to investigate other genes related to hearing loss. PMID:25992148

  18. Mutational analysis of the mitochondrial 12S rRNA and tRNA{sup Ser(UCN)} genes in Tunisian patients with nonsyndromic hearing loss

    SciTech Connect

    Mkaouar-Rebai, Emna . E-mail: emna_mkaouar@mail2world.com; Tlili, Abdelaziz; Masmoudi, Saber; Louhichi, Nacim; Charfeddine, Ilhem; Amor, Mohamed Ben; Lahmar, Imed; Driss, Nabil; Drira, Mohamed; Ayadi, Hammadi; Fakhfakh, Faiza

    2006-02-24

    We explored the mitochondrial 12S rRNA and the tRNA{sup Ser(UCN)} genes in 100 Tunisian families affected with NSHL and in 100 control individuals. We identified the mitochondrial A1555G mutation in one out of these 100 families and not in the 100 control individuals. Members of this family harbouring the A1555G mutation showed phenotypic heterogeneity which could be explained by an eventual nuclear-mitochondrial interaction. So, we have screened three nuclear genes: GJB2, GJB3, and GJB6 but we have not found correlation between the phenotypic heterogeneity and variants detected in these genes. We explored also the entire mitochondrial 12S rRNA and the tRNA{sup Ser(UCN)} genes. We detected five novel polymorphisms: T742C, T794A, A813G, C868T, and C954T, and 12 known polymorphisms in the mitochondrial 12S rRNA gene. None of the 100 families or the 100 controls were found to carry mutations in the tRNA{sup Ser(UCN)} gene. We report here First mutational screening of the mitochondrial 12S rRNA and the tRNA{sup Ser(UCN)} genes in the Tunisian population which describes the second family harbouring the A1555G mutation in Africa and reveals novel polymorphisms in the mitochondrial 12S rRNA gene.

  19. The application of genome editing in studying hearing loss.

    PubMed

    Zou, Bing; Mittal, Rahul; Grati, M'hamed; Lu, Zhongmin; Shu, Yilai; Tao, Yong; Feng, Youg; Xie, Dinghua; Kong, Weijia; Yang, Shiming; Chen, Zheng-Yi; Liu, Xuezhong

    2015-09-01

    Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The Application of Genome Editing in Studying Hearing Loss

    PubMed Central

    Zou, Bing; Mittal, Rahul; Grati, M’hamed; Lu, Zhongmin; Shu, Yilai; Tao, Yong; Feng, Youg; Xie, Dinghua; Kong, Weijia; Yang, Shiming; Chen, Zheng-Yi; Liu, Xuezhong

    2015-01-01

    Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss. PMID:25987504

  1. Can Baby Hear?

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Can Baby Hear? Past Issues / Fall 2008 Table ... to the National Institute on Deafness and Other Communication Disorders (NIDCD). Prior to this, the average age ...

  2. Living with Hearing Loss

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Living with Hearing Loss Past Issues / Fall 2008 ... the United States suffer some form of disordered communication. The National Institute on Deafness and Other Communication ...

  3. Implantable digital hearing aid

    NASA Technical Reports Server (NTRS)

    Kissiah, A. M., Jr.

    1979-01-01

    Hearing aid converts analog output of microphone into digital pulses in about 10 channels of audiofrequencies. Each pulse band could be directly connected to portion of auditory nerve most sensitive to that range.

  4. Occupational hearing loss

    MedlinePlus

    ... risks connected with recreation such as shooting a gun, driving snowmobiles, or other similar activities. Learn how ... hearing from recreational activities such as shooting a gun or driving snowmobiles. DO NOT listen to loud ...

  5. Hearing loss - infants

    MedlinePlus

    ... may not startle when there is a loud noise nearby. Older infants, who should respond to familiar ... hearing loss, such as not reacting to loud noises, not making or mimicking noises, or not speaking ...

  6. Hearing bad news.

    PubMed

    Morse, Janice

    2011-09-01

    Personal reports of receiving bad news provide data that describes patients' comprehension, reflections, experienced emotions, and an interpretative commentary with the wisdom of hindsight. Analysis of autobiographical accounts of "hearing bad news" enables the identification of patterns of how patients found out diagnoses, buffering techniques used, and styles of receiving the news. I describe how patients grapple with the news, their somatic responses to hearing, and how they struggle and strive to accept what they are hearing. I discuss metaphors used within the languages of hearing bad news. Finally, I discuss implications for a change of focus in the breaking bad news research agenda, that is, from the physician's "performance" to a patient-focused agenda.

  7. What's Hearing Loss?

    MedlinePlus

    ... regular school, or be part of a regular classroom. Depending on how severe their hearing loss is, ... read along to follow the action. Technology is changing all the time, and you will probably see ...

  8. Regional Hearing Clerk

    EPA Pesticide Factsheets

    The Regional Hearing Clerk receives filings for proceedings under the Consolidated Rules of Practice Governing the Administrative Assessment of Civil Penalties and the Revocation/Termination or Suspension of Permits, 40 Code of Federal Regulations Part 22

  9. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Reitred astronaut Lt. Gen. Thomas Stafford testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  10. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Dr. Joseph R. Fragola, Vice President, Valador, Inc., testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  11. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Jeff Hanley, Constellation Program Manager at NASA, testifies before a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  12. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Bretton Alexander, President of the Commercial Spaceflight Federation, testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  13. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Constellation Program Manager Jeff Hanley testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. Hearing AIDS and music.

    PubMed

    Chasin, Marshall; Russo, Frank A

    2004-01-01

    Historically, the primary concern for hearing aid design and fitting is optimization for speech inputs. However, increasingly other types of inputs are being investigated and this is certainly the case for music. Whether the hearing aid wearer is a musician or merely someone who likes to listen to music, the electronic and electro-acoustic parameters described can be optimized for music as well as for speech. That is, a hearing aid optimally set for music can be optimally set for speech, even though the converse is not necessarily true. Similarities and differences between speech and music as inputs to a hearing aid are described. Many of these lead to the specification of a set of optimal electro-acoustic characteristics. Parameters such as the peak input-limiting level, compression issues-both compression ratio and knee-points-and number of channels all can deleteriously affect music perception through hearing aids. In other cases, it is not clear how to set other parameters such as noise reduction and feedback control mechanisms. Regardless of the existence of a "music program,'' unless the various electro-acoustic parameters are available in a hearing aid, music fidelity will almost always be less than optimal. There are many unanswered questions and hypotheses in this area. Future research by engineers, researchers, clinicians, and musicians will aid in the clarification of these questions and their ultimate solutions.

  15. Dietary habits and hearing.

    PubMed

    Rosenhall, Ulf; Idrizbegovic, Esma; Hederstierna, Christina; Rothenberg, Elisabet

    2015-02-01

    Abstract Objective: Study groups from three age cohorts of 70-75 year-olds were investigated to search for possible correlations between dietary habits and auditory function. A cross-sectional, epidemiological study. A total number of 524 people (275 women, 249 men) were recruited from three age cohorts. The study sample was representative of the general population. All participants answered a diet history and were tested with pure-tone audiometry. Eleven categories of food consumption were related to pure-tone averages of low-mid frequency hearing, and high frequency hearing. Two consistent correlations between diet and hearing were observed. One was a correlation between good hearing and a high consumption of fish in the male group. The other was a correlation between poor high frequency hearing and a high consumption of food rich in low molecular carbohydrates in both genders; a larger effect size was seen in females. The study indicates that diet is important for aural health in aging. According to this study fish is beneficial to hearing, whereas consumption of "junk food", rich in low molecular carbohydrates, is detrimental. Other correlations, e.g. between high consumption of antioxidants, were not demonstrated here, but cannot be excluded.

  16. VOT and hearing impairment

    NASA Astrophysics Data System (ADS)

    Lane, Harlan; Perkell, Joseph

    2001-05-01

    When deafened adults recover some hearing after receiving a cochlear implant, numerous changes in their speech occur at both phonemic and suprasegmental levels. If a change toward normative values is observed for some phonemic parameter, it may be attributed to the restored hearing; however, it may be a by-product of a suprasegmental change. Consistent with results reported for speakers with normal hearing, Lane et al. [J. Acoust. Soc. Am. 98, 3096-3106 (1995)] observed in implant users that VOT varies approximately linearly with syllable duration. Therefore, in comparing pre- and postimplant measures of VOT in five speakers, each token's VOT was adjusted for the change in syllable duration of that token relative to the mean syllable duration in a baseline session (called VOTc). Preimplant, the deaf speakers characteristically uttered plosives with abnormally short VOTc. With some hearing restored, four of the five lengthened VOTc. Changes in voiced plosives' VOTc with restored hearing were correlated with changes in SPL. Some of the reliable VOTc increases that were not correlated with SPL may have been caused by auditory validation of an internal model for phoneme production. Recent studies of VOT in hearing-impaired speakers will be reviewed in this light. [Work supported by NIDCD, NIH.

  17. Hearing Aids and Music

    PubMed Central

    Chasin, Marshall; Russo, Frank A.

    2004-01-01

    Historically, the primary concern for hearing aid design and fitting is optimization for speech inputs. However, increasingly other types of inputs are being investigated and this is certainly the case for music. Whether the hearing aid wearer is a musician or merely someone who likes to listen to music, the electronic and electro-acoustic parameters described can be optimized for music as well as for speech. That is, a hearing aid optimally set for music can be optimally set for speech, even though the converse is not necessarily true. Similarities and differences between speech and music as inputs to a hearing aid are described. Many of these lead to the specification of a set of optimal electro-acoustic characteristics. Parameters such as the peak input-limiting level, compression issues—both compression ratio and knee-points—and number of channels all can deleteriously affect music perception through hearing aids. In other cases, it is not clear how to set other parameters such as noise reduction and feedback control mechanisms. Regardless of the existence of a “music program,” unless the various electro-acoustic parameters are available in a hearing aid, music fidelity will almost always be less than optimal. There are many unanswered questions and hypotheses in this area. Future research by engineers, researchers, clinicians, and musicians will aid in the clarification of these questions and their ultimate solutions. PMID:15497032

  18. Sudden hearing loss in a family with GJB2 related progressive deafness.

    PubMed

    Kokotas, Haris; Theodosiou, Maria; Korres, George; Grigoriadou, Maria; Ferekidou, Elisabeth; Giannoulia-Karantana, Aglaia; Petersen, Michael B; Korres, Stavros

    2008-11-01

    Mutations of GJB2, the gene encoding connexin 26, have been associated with prelingual, sensorineural hearing loss of mild to profound severity. One specific mutation, the 35delG, has accounted for the majority of mutations detected in the GJB2 gene in Caucasian populations. Recent studies have described progression of hearing loss in a proportion of cases with GJB2 deafness. We report an unusual family with four 35delG homozygous members, in which the parents were deaf-mute whilst both children had a postlingual progressive hearing loss. Furthermore, the son suffered from sudden hearing loss.

  19. Other Products and Devices to Improve Hearing

    MedlinePlus

    ... Products Personal Sound Amplification Products (PSAPs), or sound amplifiers, increase environmental sounds for non-hearing impaired consumers . ... FDA Consumer Update: Hearing Aids and Personal Sounds Amplifiers: Know the Difference ". More in Hearing Aids Hearing ...

  20. Restaurant noise, hearing loss, and hearing aids.

    PubMed Central

    Lebo, C P; Smith, M F; Mosher, E R; Jelonek, S J; Schwind, D R; Decker, K E; Krusemark, H J; Kurz, P L

    1994-01-01

    Our multidisciplinary team obtained noise data in 27 San Francisco Bay Area restaurants. These data included typical minimum, peak, and average sound pressure levels; digital tape recordings; subjective noise ratings; and on-site unaided and aided speech discrimination tests. We report the details and implications of these noise measurements and provide basic information on selecting hearing aids and suggestions for coping with restaurant noise. Images PMID:7941506

  1. Restaurant noise, hearing loss, and hearing aids.

    PubMed

    Lebo, C P; Smith, M F; Mosher, E R; Jelonek, S J; Schwind, D R; Decker, K E; Krusemark, H J; Kurz, P L

    1994-07-01

    Our multidisciplinary team obtained noise data in 27 San Francisco Bay Area restaurants. These data included typical minimum, peak, and average sound pressure levels; digital tape recordings; subjective noise ratings; and on-site unaided and aided speech discrimination tests. We report the details and implications of these noise measurements and provide basic information on selecting hearing aids and suggestions for coping with restaurant noise.

  2. Association of the C47T polymorphism in superoxide dismutase gene 2 with noise-induced hearing loss: a meta-analysis.

    PubMed

    Wang, Jing; Li, Jun; Peng, Kang; Fu, Zi-Ying; Tang, Jia; Yang, Ming-Jian; Chen, Qi-Cai

    Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR=0.83; 95% CI=0.63-1.09); TT vs. CC (OR=0.49; 95% CI=0.22-1.09); CT vs. CC (OR=0.54; 95% CI=0.25-1.17); TT vs. CC+CT (OR=0.82; 95% CI=0.50-1.32); CC vs. TT+TC (OR=0.49; 95% CI=0.23-1.04). However, in subgroup analysis, a significant association was found for TT vs. CC+CT (OR=0.77; 95% CI=0.42-1.41) in the Chinese population. The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association. Copyright © 2016. Published by Elsevier Editora Ltda.

  3. Conceptions of Hearing Impairment in Students.

    ERIC Educational Resources Information Center

    Alm, Irma; Ronnberg, Jerker

    1991-01-01

    Twelve students (ages 10-18) with hearing impairment and 12 normal hearing students were interviewed to determine attitudes about hearing impairment and self-concept. Results showed that school-integrated hearing-impaired students possessed a positive self-perception, but they shared normal hearing students' negative view of hearing-impaired…

  4. 18 CFR 1308.33 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Hearings. 1308.33... Prehearing and Hearing Procedures § 1308.33 Hearings. (a) TVA shall arrange for the verbatim reporting of evidentiary hearings before the Hearing Officer, and shall provide the Hearing Officer with the original...

  5. 18 CFR 1308.33 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Hearings. 1308.33... Prehearing and Hearing Procedures § 1308.33 Hearings. (a) TVA shall arrange for the verbatim reporting of evidentiary hearings before the Hearing Officer, and shall provide the Hearing Officer with the original...

  6. 13 CFR 117.16 - Hearings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Hearings. 117.16 Section 117.16... Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by § 117.15... Hearings and Appeals (OHA) that the matter be scheduled for hearing; or (2) Advise the applicant or...

  7. 13 CFR 117.16 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Hearings. 117.16 Section 117.16... Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by § 117.15... Hearings and Appeals (OHA) that the matter be scheduled for hearing; or (2) Advise the applicant or...

  8. 20 CFR 410.645 - Joint hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Joint hearings. 410.645 Section 410.645..., Finality of Decisions, and Representation of Parties § 410.645 Joint hearings. When two or more hearings... joint hearing, a joint hearing may not be held. Where joint hearings are held, a single record of the...

  9. 20 CFR 410.645 - Joint hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Joint hearings. 410.645 Section 410.645..., Finality of Decisions, and Representation of Parties § 410.645 Joint hearings. When two or more hearings... joint hearing, a joint hearing may not be held. Where joint hearings are held, a single record of the...

  10. Underwater Hearing in Turtles.

    PubMed

    Willis, Katie L

    2016-01-01

    The hearing of turtles is poorly understood compared with the other reptiles. Although the mechanism of transduction of sound into a neural signal via hair cells has been described in detail, the rest of the auditory system is largely a black box. What is known is that turtles have higher hearing thresholds than other reptiles, with best frequencies around 500 Hz. They also have lower underwater hearing thresholds than those in air, owing to resonance of the middle ear cavity. Further studies demonstrated that all families of turtles and tortoises share a common middle ear cavity morphology, with scaling best suited to underwater hearing. This supports an aquatic origin of the group. Because turtles hear best under water, it is important to examine their vulnerability to anthropogenic noise. However, the lack of basic data makes such experiments difficult because only a few species of turtles have published audiograms. There are also almost no behavioral data available (understandable due to training difficulties). Finally, few studies show what kinds of sounds are behaviorally relevant. One notable paper revealed that the Australian snake-necked turtle (Chelodina oblonga) has a vocal repertoire in air, at the interface, and under water. Findings like these suggest that there is more to the turtle aquatic auditory scene than previously thought.

  11. Hearing speech in music.

    PubMed

    Ekström, Seth-Reino; Borg, Erik

    2011-01-01

    The masking effect of a piano composition, played at different speeds and in different octaves, on speech-perception thresholds was investigated in 15 normal-hearing and 14 moderately-hearing-impaired subjects. Running speech (just follow conversation, JFC) testing and use of hearing aids increased the everyday validity of the findings. A comparison was made with standard audiometric noises [International Collegium of Rehabilitative Audiology (ICRA) noise and speech spectrum-filtered noise (SPN)]. All masking sounds, music or noise, were presented at the same equivalent sound level (50 dBA). The results showed a significant effect of piano performance speed and octave (P<.01). Low octave and fast tempo had the largest effect; and high octave and slow tempo, the smallest. Music had a lower masking effect than did ICRA noise with two or six speakers at normal vocal effort (P<.01) and SPN (P<.05). Subjects with hearing loss had higher masked thresholds than the normal-hearing subjects (P<.01), but there were smaller differences between masking conditions (P<.01). It is pointed out that music offers an interesting opportunity for studying masking under realistic conditions, where spectral and temporal features can be varied independently. The results have implications for composing music with vocal parts, designing acoustic environments and creating a balance between speech perception and privacy in social settings.

  12. Hearing is Believing

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This paper presents a discussion on the cochlear implant. This device was developed by Adam Kissiah, who suffers from hearing loss. Driven by his own hearing problem and three failed corrective surgeries, Kissiah started working in the mid-1970s on this surgically implantable device that provides hearing sensation to persons with severe-to-profound hearing loss who receive little or no benefit from hearing aids. Uniquely, the cochlear implant concept was not based on theories of medicine, as Kissiah had no medical background whatsoever. Instead, he utilized the technical expertise he learned while working as an electronics instrumentation engineer at NASA s Kennedy Space Center for the basis of his invention. This took place over 3 years, when Kissiah would spend his lunch breaks and evenings in Kennedy s technical library, studying the impact of engineering principles on the inner ear. In April of 2003, Kissiah was inducted into the Space Foundation's U.S. Space Technology Hall of Fame for his invention

  13. Noise and Hearing Loss Prevention

    MedlinePlus

    ... on Facebook Tweet Share Compartir NIOSH Sound Level Meter App Buy Quiet Program Compendium of Hearing Protection ... Publications by Topic and Type Multimedia Sound Level Meter App Search NIOSH Publications Noise and Hearing Loss ...

  14. 77 FR 64576 - Public Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-22

    ... From the Federal Register Online via the Government Publishing Office SUSQUEHANNA RIVER BASIN COMMISSION Public Hearing AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: The Susquehanna River Basin Commission will hold a public hearing on November 15, 2012, in Harrisburg...

  15. 78 FR 5556 - Public Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... From the Federal Register Online via the Government Publishing Office SUSQUEHANNA RIVER BASIN COMMISSION Public Hearing AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: The Susquehanna River Basin Commission will hold a public hearing on February 14, 2013, in Harrisburg...

  16. Noise-Induced Hearing Loss

    MedlinePlus

    ... Health Cycle Recommendations & Guidelines Free Materials Parent’s Guide Multimedia & ... Hearing plays an essential role in communication, speech and language development, and learning. Even a small amount of hearing loss can ...

  17. 78 FR 21632 - Investigative Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... hearing will be to gather additional information on the selection of the lithium ion (Li- ion) battery... compliance for the Boeing 787 Li-ion battery system. Parties to the hearing include the Federal...

  18. Could Anemia Cause Hearing Loss?

    MedlinePlus

    ... fullstory_162793.html Could Anemia Cause Hearing Loss? Iron deficiency might keep ear cells from getting oxygen ... HealthDay News) -- Hearing loss may be linked to iron deficiency anemia -- a combination of low levels of ...

  19. 78 FR 43961 - Public Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... From the Federal Register Online via the Government Publishing Office SUSQUEHANNA RIVER BASIN COMMISSION Public Hearing AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: The Susquehanna River Basin Commission will hold a public hearing on August 15, 2013, in Harrisburg,...

  20. The MYC Road to Hearing Restoration

    PubMed Central

    Kopecky, Benjamin; Fritzsch, Bernd

    2012-01-01

    Current treatments for hearing loss, the most common neurosensory disorder, do not restore perfect hearing. Regeneration of lost organ of Corti hair cells through forced cell cycle re-entry of supporting cells or through manipulation of stem cells, both avenues towards a permanent cure, require a more complete understanding of normal inner ear development, specifically the balance of proliferation and differentiation required to form and to maintain hair cells. Direct successful alterations to the cell cycle result in cell death whereas regulation of upstream genes is insufficient to permanently alter cell cycle dynamics. The Myc gene family is uniquely situated to synergize upstream pathways into downstream cell cycle control. There are three Mycs that are embedded within the Myc/Max/Mad network to regulate proliferation. The function of the two ear expressed Mycs, N-Myc and L-Myc were unknown less than two years ago and their therapeutic potentials remain speculative. In this review, we discuss the roles the Mycs play in the body and what led us to choose them to be our candidate gene for inner ear therapies. We will summarize the recently published work describing the early and late effects of N-Myc and L-Myc on hair cell formation and maintenance. Lastly, we detail the translational significance of our findings and what future work must be performed to make the ultimate hearing aid: the regeneration of the organ of Corti. PMID:24710525

  1. [Hearing disorders and rock music].

    PubMed

    Lindhardt, Bjarne Orskov

    2008-12-15

    Only few studies have investigated the frequency of hearing disorders in rock musicians. Performing rock music is apparently associated with a hearing loss in a fraction of musicians. Tinnitus and hyperacusis are more common among rock musicians than among the background population. It seems as if some sort of resistance against further hearing loss is developed over time. The use of ear protection devices have not been studied systematically but appears to be associated with diminished hearing loss.

  2. [Changes in the connexin 26 (GJB2) gene in Russian patients with hearing disorders: results of long-term molecular diagnostics of hereditary nonsyndromic deafness].

    PubMed

    Bliznets, E A; Galkina, V A; Matiushchenko, G N; Kisina, A G; Markova, T G; Poliakov, A V

    2012-01-01

    Search for mutations in the connexin 26 gene (GJB2) is a routine molecular-genetic analysis ofthe hereditary deafness worldwide. However, till now there is no assessment of the diagnostic significance of this analysis for Russian patients, and there are difficulties in interpretation of the results of DNA diagnostics. In the present study, a sample of 705 patients with nonsyndromic autosomal recessive deafness from different regions of Russian Federation was investigated. A portion of deafness like DFNB1 caused by mutations in the GJB2 gene among the sample was 46%. The frequency of deafness of such genetic type was 1:1000, that is, the frequency of isolated autosomal recessive deafness was 1:500 in the population. It was found that each sixteenth individual in Russia is a heterozygous carrier of the mutation in the GJB2gene. Totally, 20 pathological GJB2 alleles were detected; among them, a c.35delG mutation with the allelic frequency 81% prevails. Six most frequent mutations (c.35delG, c.313_326de114, c.-23+1G>A (IVS1+1G>A), c.235delC, c.167delT, and p.Glul20del), which account for 95% of pathological GJB2 alleles, were detected. Mutations previously not described in the GJB2 gene (c.129delG, p.Gly200Arg, and c[Arg127His, Gly160Ser]) were found. An optimal algorithm of molecular investigation of Russian patients which detects up to 100% of mutations in the GJB2 gene was suggested. Data concerning a clinical significance of p.Met34Thr and p.Va137Ile mutations are confirmed in the study. Eight polymorphic substitutions in the GJB2gene which do not have clinical significance (p.Va127Ile, c.*3C>A, p.Va115311e, p.Gly160Ser, c.Arg127His, p.Glull4Gly (c.341A>G), c.-45C>A, and p.Ala149Thr) were also detected.

  3. The physics of hearing: fluid mechanics and the active process of the inner ear

    NASA Astrophysics Data System (ADS)

    Reichenbach, Tobias; Hudspeth, A. J.

    2014-07-01

    Most sounds of interest consist of complex, time-dependent admixtures of tones of diverse frequencies and variable amplitudes. To detect and process these signals, the ear employs a highly nonlinear, adaptive, real-time spectral analyzer: the cochlea. Sound excites vibration of the eardrum and the three miniscule bones of the middle ear, the last of which acts as a piston to initiate oscillatory pressure changes within the liquid-filled chambers of the cochlea. The basilar membrane, an elastic band spiraling along the cochlea between two of these chambers, responds to these pressures by conducting a largely independent traveling wave for each frequency component of the input. Because the basilar membrane is graded in mass and stiffness along its length, however, each traveling wave grows in magnitude and decreases in wavelength until it peaks at a specific, frequency-dependent position: low frequencies propagate to the cochlear apex, whereas high frequencies culminate at the base. The oscillations of the basilar membrane deflect hair bundles, the mechanically sensitive organelles of the ear's sensory receptors, the hair cells. As mechanically sensitive ion channels open and close, each hair cell responds with an electrical signal that is chemically transmitted to an afferent nerve fiber and thence into the brain. In addition to transducing mechanical inputs, hair cells amplify them by two means. Channel gating endows a hair bundle with negative stiffness, an instability that interacts with the motor protein myosin-1c to produce a mechanical amplifier and oscillator. Acting through the piezoelectric membrane protein prestin, electrical responses also cause outer hair cells to elongate and shorten, thus pumping energy into the basilar membrane's movements. The two forms of motility constitute an active process that amplifies mechanical inputs, sharpens frequency discrimination, and confers a compressive nonlinearity on responsiveness. These features arise because the

  4. The physics of hearing: fluid mechanics and the active process of the inner ear.

    PubMed

    Reichenbach, Tobias; Hudspeth, A J

    2014-07-01

    Most sounds of interest consist of complex, time-dependent admixtures of tones of diverse frequencies and variable amplitudes. To detect and process these signals, the ear employs a highly nonlinear, adaptive, real-time spectral analyzer: the cochlea. Sound excites vibration of the eardrum and the three miniscule bones of the middle ear, the last of which acts as a piston to initiate oscillatory pressure changes within the liquid-filled chambers of the cochlea. The basilar membrane, an elastic band spiraling along the cochlea between two of these chambers, responds to these pressures by conducting a largely independent traveling wave for each frequency component of the input. Because the basilar membrane is graded in mass and stiffness along its length, however, each traveling wave grows in magnitude and decreases in wavelength until it peaks at a specific, frequency-dependent position: low frequencies propagate to the cochlear apex, whereas high frequencies culminate at the base. The oscillations of the basilar membrane deflect hair bundles, the mechanically sensitive organelles of the ear's sensory receptors, the hair cells. As mechanically sensitive ion channels open and close, each hair cell responds with an electrical signal that is chemically transmitted to an afferent nerve fiber and thence into the brain. In addition to transducing mechanical inputs, hair cells amplify them by two means. Channel gating endows a hair bundle with negative stiffness, an instability that interacts with the motor protein myosin-1c to produce a mechanical amplifier and oscillator. Acting through the piezoelectric membrane protein prestin, electrical responses also cause outer hair cells to elongate and shorten, thus pumping energy into the basilar membrane's movements. The two forms of motility constitute an active process that amplifies mechanical inputs, sharpens frequency discrimination, and confers a compressive nonlinearity on responsiveness. These features arise because the

  5. Upcoming hearings in Congress

    NASA Astrophysics Data System (ADS)

    The following hearings and markups have been tentatively scheduled for the coming weeks by the Senate and House of Representatives. Dates and times should be verified with the committee or subcommittee holding the hearing or markup; all offices on Capitol Hill may be reached by telephoning 202-224-3121. For guidelines on contacting a member of Congress, see AGU's Guide to Legislative Information and Contacts (Eos, August 28, 1984, p. 669).October 8: A joint hearing by the Energy Research & Development Subcommittee of the Senate Energy and Natural Resources Committee and the Nuclear Regulation Subcommittee of the Senate Environment and Public Works Committee on low-level radioactive waste (S. 1517 and S. 1578). Room SD-366, Dirksen Building, 9:30 A.M.

  6. Congenital sensorineural hearing loss

    SciTech Connect

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-02-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems.

  7. Assessment of Hearing Impaired Youth.

    ERIC Educational Resources Information Center

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  8. Assessment of Hearing Impaired Youth.

    ERIC Educational Resources Information Center

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  9. Upcoming hearing in Congress

    NASA Astrophysics Data System (ADS)

    The following hearing has been tentatively scheduled by the Senate. The date and time should be verified with the subcommittee; all congressional and committee offices may be reached by telephoning 202-224-3121. For guidelines on contacting a member of Congress, see AGU's Guide to Legislative Information and Contacts (Eos, August 28, 1984, p. 669). July 24: Hearing on the Continental Scientific Drilling and Exploration Act (S. 1026), by the Natural Resources Development and Production Subcommittee of the Senate Committee on Energy and Natural Resources. Room 366, Dirksen Senate Office Building, 10:00 A.M.

  10. Health Educators' Knowledge of Hearing, Hearing Loss, and Hearing Health Practices.

    ERIC Educational Resources Information Center

    Lass, Norman J.; And Others

    1990-01-01

    A questionnaire on hearing, hearing loss, and hearing health practices was developed and administered to 89 school health educators in 6 states. Analysis of responses indicates some deficiencies in their knowledge level suggesting the need for preservice and continuing education programs. The questionnaire is appended. (Author/DB)

  11. An introduction to hearing aids

    NASA Astrophysics Data System (ADS)

    Dyrlund, Ole

    2003-04-01

    This presentation reviews hearing-aid development from analog to advanced digital technology. A basic hearing aid consists of a microphone, an amplification circuit that provides a gain that varies with frequency to accommodate variations in hearing loss with frequency, and a small earphone. In recent years, hearing aid technology has developed rapidly. Digital hearing aids have become commonplace and their share of the marketplace is increasing rapidly. Therefore, the main focus of this talk is signal-processing schemes in advanced digital hearing aids, including microphones with digitally controlled directional characteristics, wide-dynamic-range compression in multiple channels that allow the compression characteristics to vary with frequency, noise reduction, and feedback cancellation. Each of these signal-processing functions help address the needs of individuals with hearing losses.

  12. Parent Hearing Aid Experiences

    ERIC Educational Resources Information Center

    Munoz, Karen; Roberts, Mallory; Mullings, Day; Harward, Richard

    2012-01-01

    This study addresses parent experiences in obtaining and managing hearing aids for their young child. The purpose was to identify challenges parents encounter to determine what state agencies can do to improve parent access to amplification. Data were collected July through September of 2010; 40 parents of children ages birth to 3 years old…

  13. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Dr. Karlin Toner, Director, Joint Planning and Development Office, Federal Aviation Administration (FAA), talks during a House Subcommittee on Oversight hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Dr. Edgar Waggoner, Director, Integrated Systems research Program Office, National Aeronautics and Space Administration (NASA), takes notes during a House Subcommittee on Oversight hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Dr. Edgar Waggoner, Director, Integrated Systems research Program Office, National Aeronautics and Space Administration (NASA), talks during a House Subcommittee on Oversight hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  16. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Chairman of the House Subcommittee on Oversight, U.S. Rep. Paul Broun, R-Ga, talks during a hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Ranking member of the House Subcommittee on Oversight, U.S. Rep. Dan Maffei, D-N.Y., talks during a hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  18. Parent Hearing Aid Experiences

    ERIC Educational Resources Information Center

    Munoz, Karen; Roberts, Mallory; Mullings, Day; Harward, Richard

    2012-01-01

    This study addresses parent experiences in obtaining and managing hearing aids for their young child. The purpose was to identify challenges parents encounter to determine what state agencies can do to improve parent access to amplification. Data were collected July through September of 2010; 40 parents of children ages birth to 3 years old…

  19. Sudden Hearing Loss.

    ERIC Educational Resources Information Center

    Vaughan, John C.

    1997-01-01

    Patients with a sudden dramatic decline in hearing usually require rapid diagnosis and treatment. Unfortunately, the treatment of this condition continues to be controversial and an exact etiology in most cases has been inconclusive. Nevertheless, physicians have reached a consensus regarding several broad principles, which are presented in this…

  20. Hearing, Listening and Phonosensitivity.

    ERIC Educational Resources Information Center

    Feldman, David

    This paper examines human phonosensitivity (the process by which an organism receives acoustic stimuli and integrates them into its behavior patterns), which is divided into two distinct but inseparable systems: hearing, which controls the reception, transmission, and perception of acoustic stimuli, and listening, which controls the discrimination…

  1. Hear and Now

    ERIC Educational Resources Information Center

    McKeon, Michael; Berry, Lincoln

    2006-01-01

    Classrooms often get the short shrift when it comes to designing a space that allows for optimum hearing conditions for students and speaking conditions for teachers. Over the last few years, increasing concern from state regulators and facility designers has focused greater attention on improving acoustics. The main acoustical issues to consider…

  2. Hear and Now

    ERIC Educational Resources Information Center

    McKeon, Michael; Berry, Lincoln

    2006-01-01

    Classrooms often get the short shrift when it comes to designing a space that allows for optimum hearing conditions for students and speaking conditions for teachers. Over the last few years, increasing concern from state regulators and facility designers has focused greater attention on improving acoustics. The main acoustical issues to consider…

  3. Senate Confirmation Hearing CFO

    NASA Image and Video Library

    2009-10-14

    Dr. Elizabeth M. Robinson, nominee for Chief Financial Officer for NASA, answers questions during her confirmation hearing in front of the Senate Committee on Commerce, Science and Transportation, Thursday, Oct. 15, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Paul E. Alers)

  4. Senate Confirmation Hearing CFO

    NASA Image and Video Library

    2009-10-14

    U.S. Sen. Jay Rockefeller, D-W.Va., Chairman of the of the Senate Committee on Commerce, Science and Transportation, makes a point during the nomination hearing for Dr. Elizabeth M. Robinson, nominee for Chief Financial Officer for NASA, Thursday, Oct. 15, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Paul E. Alers)

  5. Senate Confirmation Hearing IG

    NASA Image and Video Library

    2009-10-14

    Paul K. Martin, nominee for Inspector General for NASA, answers questions during his confirmation hearing in front of the Senate Committee on Commerce, Science and Transportation, Thursday, Oct. 15, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Paul E. Alers)

  6. Senate Confirmation Hearing CFO

    NASA Image and Video Library

    2009-10-14

    U.S. Sen. Maria Cantwell, D-Wash., left, talks about Dr. Elizabeth M. Robinson, nominee for Chief Financial Officer for NASA, right, prior to her confirmation hearing in front of the Senate Committee on Commerce, Science and Transportation, Thursday, Oct. 15, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Paul E. Alers)

  7. Senate Confirmation Hearing IG

    NASA Image and Video Library

    2009-10-14

    Paul K. Martin, nominee for Inspector General at NASA, right, answers questions during his confirmation hearing in front of the Senate Committee on Commerce, Science and Transportation, Thursday, Oct. 15, 2009, on Capitol Hill in Washington. At left is Dr. Elizabeth M. Robinson, nominee for Chief Financial Officer for NASA. Photo Credit: (NASA/Paul E. Alers)

  8. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Bryan O'Connor, Chief of Safety and Mission Assurance at NASA, testifies before a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  9. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    U.S. Rep. Pete Olson, R-Texas, speaks during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  10. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    Bryan O'Connor, Chief of Safety and Mission Assurance at NASA, testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  11. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    U.S. Rep. Gabrielle Giffords, D-Ariz., left, speaks with reitred astronaut Lt. Gen. Thomas Stafford prior to the start of a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  12. Human Spaceflight Safety Hearing

    NASA Image and Video Library

    2009-12-02

    John Marshall, a member of the NASA Aerospace Safety Advisory Panel (ASAP), testifies during a hearing before the House Subcommitte on Space and Aeronautics regarding Safety of Human Spaceflight on Capitol Hill, Wednesday, Dec. 2, 2009, in Washington. Photo Credit: (NASA/Bill Ingalls)

  13. Unmanned Aircraft House Hearing

    NASA Image and Video Library

    2013-02-15

    Dr. Gerald Dillingham, Director, Civil Aviation Issues, Government Accounting Office (GAO), talks during a House Subcommittee on Oversight hearing titled "Operating Unmanned Aircraft Systems in the National Airspace System: Assessing Research and Development Efforts to Ensure Safety" on Friday, Feb. 15, 2013 at the Rayburn House Office Building in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    NASA Administrator Dr. Michael Griffin smiles during his appearance in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. Lori Garver Confirmation Hearing

    NASA Image and Video Library

    2009-07-07

    Charles Bolden, nominee for Administrator of NASA, left, and Lori Garver, Nominee for Deputy Administrator of NASA, testify at their confirmation hearing before the Senate Commerce, Science and Transportation Committee in the Russell Senate Office Building on Capitol Hill in Washington, Wednesday, July 8, 2009. Photo Credit: (NASA/Bill Ingalls)

  16. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Elizabeth Robinson, NASA Chief Finiancial Officer, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Elizabeth Robinson, NASA Chief Financial Officer, far right, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  18. Lori Garver Confirmation Hearing

    NASA Image and Video Library

    2009-07-07

    Lori Garver, nominee for Deputy Administrator of NASA, testifies at her confirmation hearing before the Senate Commerce, Science and Transportation Committee in the Russell Senate Office Building on Capitol Hill in Washington, Wednesday, July 8, 2009. Photo Credit: (NASA/Bill Ingalls)

  19. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Paul Martin, Inspector General for NASA, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  20. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Thomas Howard, NASA Deputy Inspector General, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  1. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    NASA Administrator Dr. Michael Griffin is seen during his appearance in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  2. Independent Audit House Hearing

    NASA Image and Video Library

    2009-12-03

    Elizabeth Robinson, NASA Chief Financial Officer, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  3. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    NASA Administrator Dr. Michael Griffin is seen prior to his appearance in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  4. Charles Bolden Confirmation Hearing

    NASA Image and Video Library

    2009-07-07

    Charles Bolden, nominee for Administrator of NASA, left, and Lori Garver, nominee for Deputy Administrator of NASA, listen to Senators questions at their confirmation hearing before the Senate Commerce, Science and Transportation Committee in the Russell Senate Office Building on Capitol Hill in Washington, Wednesday, July 8, 2009. Photo Credit: (NASA/Bill Ingalls)

  5. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    NASA Administrator Dr. Michael Griffin speaks in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  6. Charles Bolden Confirmation Hearing

    NASA Image and Video Library

    2009-07-07

    Charles Bolden, nominee for Administrator of NASA, testifies at his confirmation hearing before the Senate Commerce, Science and Transportation Committee in the Russell Senate Office Building on Capitol Hill in Washington, Wednesday, July 8, 2009. Photo Credit: (NASA/Bill Ingalls)

  7. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    NASA Administrator Dr. Michael Griffin delivers a statement during testimony in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  8. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Daniel Murrin, Partner, Assurance and Advisory Business Services, Ernst & Young LLP, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  9. House Hearing Independent Audit

    NASA Image and Video Library

    2009-12-03

    Daniel Murrin, Partner, Assurance and Advisory Business Service, Ernst & Young LLP, testifies during a Joint Hearing before the House Committee on Science and Technology, Transportation and Infrastructure Committee, Subcommittee on Investigations and Oversight, Thursday, Dec. 3, 2009, on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  10. Michael Griffin Senate Hearing

    NASA Image and Video Library

    2005-05-17

    Senator Trent Lott, R-Miss., questions NASA Administrator Dr. Michael Griffin during his appearance in front of the Senate Commerce Committee Science and Space Subcommittee hearing on Human Space Flight: The Space Shuttle and Beyond, Wednesday, May 18, 2005, in the Russell Senate Office Building on Capitol Hill in Washington. Photo Credit: (NASA/Bill Ingalls)

  11. Charles Bolden Confirmation Hearing

    NASA Image and Video Library

    2009-07-07

    Charles Bolden, nominee for Administrator of NASA, waits for his turn to testify at his confirmation hearing before the Senate Commerce, Science and Transportation Committee in the Russell Senate Office Building on Capitol Hill in Washington, Wednesday, July 8, 2009. Photo Credit: (NASA/Bill Ingalls)

  12. Sudden Hearing Loss.

    ERIC Educational Resources Information Center

    Vaughan, John C.

    1997-01-01

    Patients with a sudden dramatic decline in hearing usually require rapid diagnosis and treatment. Unfortunately, the treatment of this condition continues to be controversial and an exact etiology in most cases has been inconclusive. Nevertheless, physicians have reached a consensus regarding several broad principles, which are presented in this…

  13. Hearing disorders in cats.

    PubMed

    Strain, George M

    2017-03-01

    Practical relevance: Auditory function is a sense that is central to life for cats - being important in situational awareness of potential predators, pursuit of prey, and for communication with conspecifics, humans and other species. Deafness in cats is most frequently the result of a genetic disorder, strongly associated with white fur and blue eyes, but may also result from acquired causes such as advancing age, ototoxic drugs, infection, environmental noise and physical trauma. Deafness can be sensorineural, where there is loss of cochlear hair cells, or conductive, where sound is muffled on its way to the inner ear. Clinical challenges: Establishing whether a cat is deaf can be difficult as behavioral testing of hearing is subjective and does not reliably detect unilateral deafness. Brainstem auditory evoked response testing is an objective measure but is limited in its availability. Currently, sensorineural deafness is irreversible because no treatments are available to restore lost hair cells. Conductive hearing loss can usually be treated, although full hearing recovery following otitis media may take weeks as the body clears the middle ear of debris. Evidence base: The author draws on the published literature and his extensive research on clinical aspects and molecular genetics of deafness, principally in companion animals, to review types and forms of deafness in cats. He also discusses current diagnostic approaches and provides brief advice for managing cats with hearing loss.

  14. Value of genetic testing in the otological approach for sensorineural hearing loss.

    PubMed

    Matsunaga, Tatsuo

    2009-12-01

    Sensorineural hearing loss (SNHL) is one of the most common disabilities in human, and genetics is an important aspect for SNHL, especially in children. In recent 10 years, our knowledge in genetic causes of SNHL has made a significant advance, and now it is used for diagnosis and other clinical practices. Hereditary hearing loss can be classified into syndromic and nonsyndromic hearing loss. As the nonsyndromic deafness genes, more than 100 loci for deafness genes have been determined, and more than 40 genes were identified. Furthermore, more than 300 forms of syndromic hearing loss have been characterized, and each syndrome may have several causative genes. In childhood hearing loss, early educational intervention is required in addition to medical intervention for normal development of speech and language. In addition, even severe to profound hearing loss may be restored very effectively by hearing aids or cochlear implants. Because of these features of SNHL, genetic testing has exceptionally high value in the medical practice for hereditary hearing loss. Several strategies are used for genetic testing of SNHL for accurate and efficient identification of the genetic causes, and the results were used for explanation of the cause, prediction of auditory features, prevention of deafness, management of associated symptoms, determination of therapy, and genetic counseling. Identification of damaged cells in the inner ear and the underlying mechanism by genetic testing undoubtedly facilitates development and introduction of novel and specific therapies to distinct types of SNHL.

  15. Hereditary non-syndromic sensorineural hearing loss: transforming silence to sound.

    PubMed

    Schrijver, Iris

    2004-11-01

    Tremendous progress has been made in our understanding of the molecular basis of hearing and hearing loss. Through recent advances, we have begun to understand the fascinating biology of the auditory system and unveiled new molecular mechanisms of hearing impairment. Changes in the diagnostic impact of genetic testing have occurred, as well as exciting developments in therapeutic options. Molecular diagnosis, which is already a reality for several hearing-associated genes, will doubtlessly continue to increase in the near future, both in terms of the number of mutations tested and the spectrum of genes. Genetic analysis for hearing loss is mostly used for diagnosis and treatment, and relatively rarely for reproductive decisions, in contrast to other inherited disorders. Inherited hearing loss, however, is characterized by impressive genetic heterogeneity. An abundance of genes carry a large number of mutations, but specific mutations in a single gene may lead to syndromic or non-syndromic hearing loss. Some mutations predominate in individual ethnic groups. For clinical and laboratory diagnosticians, it is challenging to keep abreast of the unfolding discoveries. This review aims to provide the framework pertinent to diagnosticians and a practical approach to mutation analysis in the hearing impaired.

  16. Hearing aids for mild to moderate hearing loss in adults.

    PubMed

    Ferguson, Melanie A; Kitterick, Pádraig T; Chong, Lee Yee; Edmondson-Jones, Mark; Barker, Fiona; Hoare, Derek J

    2017-09-25

    The main clinical intervention for mild to moderate hearing loss is the provision of hearing aids. These are routinely offered and fitted to those who seek help for hearing difficulties. By amplifying and improving access to sounds, and speech sounds in particular, the aim of hearing aid use is to reduce the negative consequences of hearing loss and improve participation in everyday life. To evaluate the effects of hearing aids for mild to moderate hearing loss in adults. The Cochrane ENT Information Specialist searched the ENT Trials Register; the Cochrane Register of Studies Online; MEDLINE; PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 March 2017. Randomised controlled trials (RCTs) of hearing aids compared to a passive or active control in adults with mild to moderate hearing loss. We used the standard methodological procedures expected by Cochrane. The primary outcomes in this review were hearing-specific health-related quality of life and the adverse effect pain. Secondary outcomes were health-related quality of life, listening ability and the adverse effect noise-induced hearing loss. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. We included five RCTs involving 825 participants. The studies were carried out in the USA and Europe, and were published between 1987 and 2017. Risk of bias across the studies varied. Most had low risk for selection, reporting and attrition bias, and a high risk for performance and detection bias because blinding was inadequate or absent.All participants had mild to moderate hearing loss. The average age across all five studies was between 69 and 83 years. The duration of the studies ranged between six weeks and six months.There was a large beneficial effect of hearing aids on hearing-specific health-related quality of life associated with participation in daily life as

  17. Genetics of Hearing Loss – Syndromic

    PubMed Central

    Koffler, Tal; Ushakov, Kathy; Avraham, Karen B.

    2015-01-01

    Synopsis Hearing loss (HL) is one of the most common birth defects in developed countries and is a diverse pathology with different classifications. One of these is based on the association with other clinical features, defined as syndromic hearing loss (SHL). Determining the etiology of the HL in these patients is extremely beneficial as it enables a personalized approach to caring for the individual. Early screening can further aid in optimal rehabilitation for a child’s development and growth. Pathogenic variants in forty-five genes, encoding proteins functioning as ion channels, transcription factors, molecular motors and more, are known to lead to eleven forms of SHL. The development of high-throughput sequencing technology is facilitating rapid and low-cost diagnostics for patients with SHL. PMID:26443487

  18. Study of a Brazilian family presenting non-syndromic hearing loss with mitochondrial inheritance.

    PubMed

    Pupo, Altair Cadrobbi; Pirana, Sulene; Spinelli, Mauro; Lezirovitz, Karina; Mingroni Netto, Regina C; Macedo, Lisandra S

    2008-01-01

    We hereby report on the audiological and genetic findings in individuals from a Brazilian family, with the following mitochondrial mutation A1555G in the 12SrRNA gene (MT-RNR-1). Nine individuals underwent speech, audiologic (tonal audiometry and logoaudiometry) and genetic evaluations. Eight individuals among the A1555G carriers were affected by hearing impairment and one person had normal hearing thresholds till the end of the present study. The audiologic evaluation results indicated normal hearing thresholds all the way to bilateral profound hearing loss with post-lingual onset and variable configuration. Two affected siblings presented progressive hearing loss. It was impossible to precise the time of hearing loss onset; however, the impairment was present in both children and adults. The genetic study revealed the A1555G mitochondrial mutation in the 12SrRNA gene. Given the prevalence of mitochondrial mutations as a cause of hearing loss, it is fundamental to perform the etiopathologic diagnosis in order to postpone the onset or avoid hearing impairment progression. This kind of hearing impairment represents a challenge to the professionals since there are no physical traits that indicate genetic transmission.

  19. 10 CFR 2.1308 - Oral hearings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Oral hearings. 2.1308 Section 2.1308 Energy NUCLEAR REGULATORY COMMISSION AGENCY RULES OF PRACTICE AND PROCEDURE Procedures for Hearings on License Transfer Applications § 2.1308 Oral hearings. Hearings under this subpart will be oral hearings, unless, within 15...

  20. 10 CFR 2.1308 - Oral hearings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Oral hearings. 2.1308 Section 2.1308 Energy NUCLEAR REGULATORY COMMISSION AGENCY RULES OF PRACTICE AND PROCEDURE Procedures for Hearings on License Transfer Applications § 2.1308 Oral hearings. Hearings under this subpart will be oral hearings, unless, within 15...

  1. 40 CFR 57.807 - Hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Hearing. 57.807 Section 57.807... § 57.807 Hearing. (a) Composition of hearing panel. The Presiding Officer shall preside at the hearing held under this subpart. An EPA panel shall also take part in the hearing. In general, the membership...

  2. 18 CFR 1302.9 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Hearings. 1302.9... Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by § 1302.7(b... notice within which the recipient may request of TVA that the matter be scheduled for hearing or (2...

  3. 22 CFR 34.15 - Outside hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and location of the hearing. If the hearing will be paper, the employee shall be notified that he or... need not take the form of an evidentiary hearing. (3) Paper hearing. If the hearing official determines... the indebtedness through alternative collection methods under § 34.10. ...

  4. 22 CFR 34.15 - Outside hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and location of the hearing. If the hearing will be paper, the employee shall be notified that he or... need not take the form of an evidentiary hearing. (3) Paper hearing. If the hearing official determines... the indebtedness through alternative collection methods under § 34.10. ...

  5. 10 CFR 205.172 - Hearings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Hearings. (a) The DOE in its discretion may direct that a hearing be convened on its own initiative or upon... determination as to who may attend a hearing convened under this subpart shall be in the discretion of DOE, but a hearing will usually not be open to the public. Where the hearing involves a matter arising...

  6. 10 CFR 2.1507 - Oral hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Oral hearing. 2.1507 Section 2.1507 Energy NUCLEAR... Hearings § 2.1507 Oral hearing. (a) Not less than five (5) days before the commencement of the oral hearing... witnesses at the oral hearing. The order shall be filed upon all participants by email or facsimile...

  7. 10 CFR 1003.62 - Hearings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Hearings. 1003.62 Section 1003.62 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICE OF HEARINGS AND APPEALS PROCEDURAL REGULATIONS Conferences and Hearings § 1003.62 Hearings. (a) The OHA in its discretion may direct that a hearing be convened on its own...

  8. 34 CFR 668.116 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Hearing. 668.116 Section 668.116 Education Regulations... Program Review Determinations § 668.116 Hearing. (a) A hearing is a process conducted by the hearing official whereby an orderly presentation of arguments and evidence is made by the parties. (b) The hearing...

  9. 5 CFR 1215.5 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

  10. 29 CFR 1450.22 - Hearing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Hearing. 1450.22 Section 1450.22 Labor Regulations Relating... STATES Salary Offset § 1450.22 Hearing. (a) Petition for hearing. (1) A hearing may be requested by..., and is not accepted pursuant to paragraph (a)(4) of this section, the employee's right to hearing will...

  11. 10 CFR 431.426 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Hearing. 431.426 Section 431.426 Energy DEPARTMENT OF... § 431.426 Hearing. The Secretary may hold a public hearing, and publish notice in the Federal Register of the date and location of the hearing, when he determines that such a hearing is necessary and...

  12. 5 CFR 1215.5 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

  13. 45 CFR 73b.5 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Hearings. 73b.5 Section 73b.5 Public Welfare... § 73b.5 Hearings. (a) Hearings shall be stenographically recorded and transcribed and the testimony of witnesses shall be taken under oath or affirmation. Hearings will be closed unless an open hearing is...

  14. 45 CFR 16.11 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Hearing. 16.11 Section 16.11 Public Welfare... BOARD § 16.11 Hearing. (a) Electing a hearing. If the appellant believes a hearing is appropriate, the... appeal file). The Board will approve a request (and may schedule a hearing on its own or in response to a...

  15. 44 CFR 7.13 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Hearings. 7.13 Section 7.13... Programs-General § 7.13 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is... may request of the responsible agency official that the matter be scheduled for hearing or (2) advise...

  16. 44 CFR 7.13 - Hearings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Hearings. 7.13 Section 7.13... Programs-General § 7.13 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is... may request of the responsible agency official that the matter be scheduled for hearing or (2) advise...

  17. 18 CFR 1302.9 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Hearings. 1302.9... Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by § 1302.7(b... notice within which the recipient may request of TVA that the matter be scheduled for hearing or (2...

  18. 39 CFR 957.13 - Hearings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Hearings. 957.13 Section 957.13 Postal Service... SUSPENSION FROM CONTRACTING § 957.13 Hearings. (a) Hearings are held at 2101 Wilson Boulevard, Suite 600... than 7 days prior to the scheduled date of a hearing, file a request that such hearing be held at a...

  19. 49 CFR 209.115 - Hearing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Hearing. 209.115 Section 209.115 Transportation... Hearing. (a) When a hearing is requested and scheduled under § 209.113, a hearing officer designated by the Chief Counsel convenes and presides over the hearing. If requested by respondent and if...

  20. 29 CFR 2700.108 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Hearing. 2700.108 Section 2700.108 Labor Regulations... Proceedings § 2700.108 Hearing. (a) Procedures. As soon as practicable after the conclusion of the pre-hearing conference, the Judge will hold a hearing on any issue that remains in dispute. The hearing will be in...

  1. 28 CFR 42.109 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Hearings. 42.109 Section 42.109 Judicial....109 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by § 42... that the responsible Department official schedule the matter for hearing, or (2) advise the applicant...

  2. 45 CFR 1203.9 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Hearings. 1203.9 Section 1203.9 Public Welfare... Hearings. (a) Opportunity for hearing. When an opportunity for a hearing is required by § 1203.8(c... matter be scheduled for hearing; or (2) Advise the applicant or recipient that the matter in question has...

  3. 39 CFR 957.13 - Hearings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Hearings. 957.13 Section 957.13 Postal Service... SUSPENSION FROM CONTRACTING § 957.13 Hearings. (a) Hearings are held at 2101 Wilson Boulevard, Suite 600... than 7 days prior to the scheduled date of a hearing, file a request that such hearing be held at a...

  4. 12 CFR 308.164 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Hearings. 308.164 Section 308.164 Banks and... Where a Felony ls Charged § 308.164 Hearings. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 30 days after receipt of a request for hearing filed pursuant to § 308.163...

  5. 29 CFR 2700.108 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Hearing. 2700.108 Section 2700.108 Labor Regulations... Proceedings § 2700.108 Hearing. (a) Procedures. As soon as practicable after the conclusion of the pre-hearing conference, the Judge will hold a hearing on any issue that remains in dispute. The hearing will be in...

  6. 34 CFR 668.88 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Hearing. 668.88 Section 668.88 Education Regulations of... Proceedings § 668.88 Hearing. (a) A hearing is an orderly presentation of arguments and evidence conducted by a hearing official. (b) If the hearing official, the designated department official who brought a...

  7. 12 CFR 308.160 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Hearings. 308.160 Section 308.160 Banks and... Hearings. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 60 days after receipt of a request for hearing on an application filed pursuant to § 308.159. Upon the request...

  8. 7 CFR 400.132 - Hearings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Hearings. 400.132 Section 400.132 Agriculture... Years § 400.132 Hearings. (a) If an employee timely files a petition for a hearing, the FCIC Official will select the date, time, and location for the hearing. (b) The hearing shall be conducted by an...

  9. 10 CFR 1003.62 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Hearings. 1003.62 Section 1003.62 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICE OF HEARINGS AND APPEALS PROCEDURAL REGULATIONS Conferences and Hearings § 1003.62 Hearings. (a) The OHA in its discretion may direct that a hearing be convened on its own...

  10. 17 CFR 204.64 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Hearing. 204.64 Section 204.64... Administrative Wage Garnishment § 204.64 Hearing. (a) Request for hearing. The Commission will order a hearing... hearing concerning, for debts not previously established by judicial or administrative order, the...

  11. 5 CFR 1215.5 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

  12. 15 CFR 8.12 - Hearings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Hearings. 8.12 Section 8.12 Commerce... Compliance § 8.12 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by... hearing, or (2) advise the recipient or other party that the matter in question has been set down for...

  13. 19 CFR 356.23 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Hearing. 356.23 Section 356.23 Customs Duties... § 356.23 Hearing. (a) Scheduling of hearing. The administrative law judge will schedule the hearing at a... parties adequately to prepare for the hearing and the importance of expeditiously resolving the matter. (b...

  14. 12 CFR 308.164 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Hearings. 308.164 Section 308.164 Banks and... Where a Felony ls Charged § 308.164 Hearings. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 30 days after receipt of a request for hearing filed pursuant to § 308.163...

  15. 29 CFR 1450.22 - Hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Hearing. 1450.22 Section 1450.22 Labor Regulations Relating... STATES Salary Offset § 1450.22 Hearing. (a) Petition for hearing. (1) A hearing may be requested by..., and is not accepted pursuant to paragraph (a)(4) of this section, the employee's right to hearing will...

  16. 15 CFR 8.12 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Hearings. 8.12 Section 8.12 Commerce... Compliance § 8.12 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by... hearing, or (2) advise the recipient or other party that the matter in question has been set down for...

  17. 5 CFR 1215.5 - Hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

  18. 40 CFR 57.807 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Hearing. 57.807 Section 57.807... § 57.807 Hearing. (a) Composition of hearing panel. The Presiding Officer shall preside at the hearing held under this subpart. An EPA panel shall also take part in the hearing. In general, the membership...

  19. 36 CFR 1211.620 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Hearings. 1211.620 Section... Procedures § 1211.620 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is... may request of the designated agency official that the matter be scheduled for hearing; or (2) Advise...

  20. 49 CFR 209.115 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Hearing. 209.115 Section 209.115 Transportation... Hearing. (a) When a hearing is requested and scheduled under § 209.113, a hearing officer designated by the Chief Counsel convenes and presides over the hearing. If requested by respondent and if...

  1. 10 CFR 431.426 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Hearing. 431.426 Section 431.426 Energy DEPARTMENT OF... § 431.426 Hearing. The Secretary may hold a public hearing, and publish notice in the Federal Register of the date and location of the hearing, when he determines that such a hearing is necessary and...

  2. 12 CFR 308.160 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Hearings. 308.160 Section 308.160 Banks and... Hearings. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 60 days after receipt of a request for hearing on an application filed pursuant to § 308.159. Upon the request...

  3. 10 CFR 205.172 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Hearings. 205.172 Section 205.172 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Conferences, Hearings, and Public Hearings § 205.172 Hearings. (a) The DOE in its discretion may direct that a hearing be convened on its own initiative or upon...

  4. 41 CFR 105-57.005 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Hearing. 105-57.005...-ADMINISTRATION WAGE GARNISHMENT § 105-57.005 Hearing. (a) GSA will provide a hearing, which at the hearing... by GSA, the debtor submits a signed and dated written request for a hearing, to the official named in...

  5. 19 CFR 111.67 - Hearing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Hearing. 111.67 Section 111.67 Customs Duties U.S... Revocation § 111.67 Hearing. (a) Hearing officer. The hearing officer must be an administrative law judge... right to examine all exhibits offered at the hearing and will have the right to cross-examine witnesses...

  6. 15 CFR 8.12 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Hearings. 8.12 Section 8.12 Commerce... Compliance § 8.12 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required by... hearing, or (2) advise the recipient or other party that the matter in question has been set down for...

  7. 37 CFR 11.44 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Hearings. 11.44 Section 11.44... Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.44 Hearings. (a) The hearing officer shall preside over hearings in disciplinary proceedings. The hearing officer shall set the time...

  8. 22 CFR 512.21 - Hearing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Hearing. 512.21 Section 512.21 Foreign Relations....21 Hearing. (a) Petition for hearing. (1) A hearing may be requested by filing a written petition... section, the employee's right to hearing will be considered waived, and salary offset will be implemented...

  9. 45 CFR 16.11 - Hearing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Hearing. 16.11 Section 16.11 Public Welfare... BOARD § 16.11 Hearing. (a) Electing a hearing. If the appellant believes a hearing is appropriate, the... appeal file). The Board will approve a request (and may schedule a hearing on its own or in response to a...

  10. 7 CFR 400.132 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Hearings. 400.132 Section 400.132 Agriculture... Years § 400.132 Hearings. (a) If an employee timely files a petition for a hearing, the FCIC Official will select the date, time, and location for the hearing. (b) The hearing shall be conducted by an...

  11. 12 CFR 308.155 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Hearing. 308.155 Section 308.155 Banks and... Pursuant to Section 32 of the FDIA § 308.155 Hearing. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 30 days after receipt of a request for a hearing filed pursuant...

  12. 45 CFR 16.11 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Hearing. 16.11 Section 16.11 Public Welfare... BOARD § 16.11 Hearing. (a) Electing a hearing. If the appellant believes a hearing is appropriate, the... appeal file). The Board will approve a request (and may schedule a hearing on its own or in response to a...

  13. 29 CFR 2700.108 - Hearing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Hearing. 2700.108 Section 2700.108 Labor Regulations... Proceedings § 2700.108 Hearing. (a) Procedures. As soon as practicable after the conclusion of the pre-hearing conference, the Judge will hold a hearing on any issue that remains in dispute. The hearing will be in...

  14. 22 CFR 512.21 - Hearing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Hearing. 512.21 Section 512.21 Foreign... Offset § 512.21 Hearing. (a) Petition for hearing. (1) A hearing may be requested by filing a written... section, the employee's right to hearing will be considered waived, and salary offset will be implemented...

  15. 37 CFR 11.44 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Hearings. 11.44 Section 11.44... Proceedings; Jurisdiction, Sanctions, Investigations, and Proceedings § 11.44 Hearings. (a) The hearing officer shall preside over hearings in disciplinary proceedings. The hearing officer shall set the time...

  16. 12 CFR 308.155 - Hearing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Hearing. 308.155 Section 308.155 Banks and... Pursuant to Section 32 of the FDIA § 308.155 Hearing. (a) Hearing dates. The Executive Secretary shall order a hearing to be commenced within 30 days after receipt of a request for a hearing filed pursuant...

  17. 45 CFR 611.9 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Hearings. 611.9 Section 611.9 Public Welfare... 1964 § 611.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is required... recipient may request of the responsible Foundation official that the matter be scheduled for hearing or (2...

  18. 7 CFR 400.132 - Hearings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Hearings. 400.132 Section 400.132 Agriculture... Years § 400.132 Hearings. (a) If an employee timely files a petition for a hearing, the FCIC Official will select the date, time, and location for the hearing. (b) The hearing shall be conducted by an...

  19. 36 CFR 1211.620 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Hearings. 1211.620 Section... Procedures § 1211.620 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is... may request of the designated agency official that the matter be scheduled for hearing; or (2) Advise...

  20. 44 CFR 7.13 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Hearings. 7.13 Section 7.13... Programs-General § 7.13 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a hearing is... may request of the responsible agency official that the matter be scheduled for hearing or (2) advise...