Last Sunday’s (8/14/2016) Washington Post article on hearing loss and hearing aids cites the NIDCD, HLAA, AARP, and PCAST, but none of the professional associations (including the Academy) were asked to comment on the topic. Dr.
This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr. 18 (peak SNP rs29632020), one gene, deleted in colorectal carcinoma (Dcc) has a well-established role in nervous system development. An in-depth analysis of Dcc-deficient mice demonstrated elevation in mean VsEP threshold for Dcc +/− mice (−11.86 dB) compared to wild-type (−9.68 dB) littermates. Synaptic ribbon studies revealed Dcc −/− (P0) and Dcc +/− (6-week-old) mice showed lower density of the presynaptic marker (CtBP2) as compared to wild-type controls. Vestibular ganglion cell counts of Dcc −/− (P0) was lower than controls. Whole-mount preparations showed abnormal innervation of the utricle, saccule, and crista ampullaris at E14.5, E16.5, and E18.5. Postnatal studies were limited by the perinatal lethality in Dcc −/− mice. Expression analyses using in situ hybridization and immunohistochemistry showed Dcc expression in the mouse vestibular ganglion (E15.5), and utricle and crista ampullaris (6-week-old), respectively. In summary, we report the first GWAS for vestibular functional variation in inbred mice and provide evidence for the role of Dcc in the normal innervation of the peripheral vestibular system.
Comparative auditory studies make it possible both to understand the origins of modern ears and the factors underlying the similarities and differences in their performance. After all lineages of land vertebrates had independently evolved tympanic middle ears in the early Mesozoic era, the subsequent tens of millions of years led to the hearing organ of lizards, birds, and mammals becoming larger and their upper frequency limits higher. In extant species, lizard papillae remained relatively small (<2 mm), but avian papillae attained a maximum length of 11 mm, with the highest frequencies in both groups near 12 kHz. Hearing-organ sizes in modern mammals vary more than tenfold, up to >70 mm (made possible by coiling), as do their upper frequency limits (from 12 to >200 kHz). The auditory organs of the three amniote groups differ characteristically in their cellular structure, but their hearing sensitivity and frequency selectivity within their respective hearing ranges hardly differ. In the immediate primate ancestors of humans, the cochlea became larger and lowered its upper frequency limit. Modern humans show an unusual trend in frequency selectivity as a function of frequency. It is conceivable that the frequency selectivity patterns in humans were influenced in their evolution by the development of speech.
Wideband acoustic immittance measurements in assessing crimping status following stapedotomy: A temporal bone study.
Int J Audiol. 2016 Aug 18;:1-7
Authors: Wegner I, Shahnaz N, Grolman W, Bance ML
Abstract
OBJECTIVE: To ascertain if wideband acoustic immitance (WAI) measurements are useful in assessing crimping status following stapedotomy.
DESIGN: WAI measurements were obtained using the Mimosa Acoustics HearID system. Wideband chirp sound stimuli and a set of tone stimuli for nine frequencies between 0.2 and 6 kHz were used at 60 dB SPL. Five sets of measurements were performed on each temporal bone: mobile stapes, stapes fixation and stapedotomy followed by insertion of a tightly crimped, a loosely crimped and an uncrimped prosthesis.
STUDY SAMPLE: Eight fresh-frozen temporal bones were harvested from human cadaveric donors.
RESULTS: At lower frequencies, up to 1 kHz, stapes fixation decreased absorbance. Compared to the baseline absorbance, absorbance with stapes fixation dropped by 6 to 17% in absolute terms from the baseline value (p = 0.027). Absorbance was not affected in higher frequencies (p = 0.725). Stapedotomy changed the absorbance curve significantly compared to the normal condition with an increase of absolute absorbance values by 6 to 36% around 0.25-1 kHz (p-value <0.01). The crimping conditions did not differ from one another (p = 0.555).
CONCLUSION: WAI is not useful in distinguishing between tightly crimped, loosely crimped and uncrimped stapes prostheses following stapedotomy.
PMID: 27534272 [PubMed - as supplied by publisher]
Wideband acoustic immittance measurements in assessing crimping status following stapedotomy: A temporal bone study.
Int J Audiol. 2016 Aug 18;:1-7
Authors: Wegner I, Shahnaz N, Grolman W, Bance ML
Abstract
OBJECTIVE: To ascertain if wideband acoustic immitance (WAI) measurements are useful in assessing crimping status following stapedotomy.
DESIGN: WAI measurements were obtained using the Mimosa Acoustics HearID system. Wideband chirp sound stimuli and a set of tone stimuli for nine frequencies between 0.2 and 6 kHz were used at 60 dB SPL. Five sets of measurements were performed on each temporal bone: mobile stapes, stapes fixation and stapedotomy followed by insertion of a tightly crimped, a loosely crimped and an uncrimped prosthesis.
STUDY SAMPLE: Eight fresh-frozen temporal bones were harvested from human cadaveric donors.
RESULTS: At lower frequencies, up to 1 kHz, stapes fixation decreased absorbance. Compared to the baseline absorbance, absorbance with stapes fixation dropped by 6 to 17% in absolute terms from the baseline value (p = 0.027). Absorbance was not affected in higher frequencies (p = 0.725). Stapedotomy changed the absorbance curve significantly compared to the normal condition with an increase of absolute absorbance values by 6 to 36% around 0.25-1 kHz (p-value <0.01). The crimping conditions did not differ from one another (p = 0.555).
CONCLUSION: WAI is not useful in distinguishing between tightly crimped, loosely crimped and uncrimped stapes prostheses following stapedotomy.
PMID: 27534272 [PubMed - as supplied by publisher]
Wideband acoustic immittance measurements in assessing crimping status following stapedotomy: A temporal bone study.
Int J Audiol. 2016 Aug 18;:1-7
Authors: Wegner I, Shahnaz N, Grolman W, Bance ML
Abstract
OBJECTIVE: To ascertain if wideband acoustic immitance (WAI) measurements are useful in assessing crimping status following stapedotomy.
DESIGN: WAI measurements were obtained using the Mimosa Acoustics HearID system. Wideband chirp sound stimuli and a set of tone stimuli for nine frequencies between 0.2 and 6 kHz were used at 60 dB SPL. Five sets of measurements were performed on each temporal bone: mobile stapes, stapes fixation and stapedotomy followed by insertion of a tightly crimped, a loosely crimped and an uncrimped prosthesis.
STUDY SAMPLE: Eight fresh-frozen temporal bones were harvested from human cadaveric donors.
RESULTS: At lower frequencies, up to 1 kHz, stapes fixation decreased absorbance. Compared to the baseline absorbance, absorbance with stapes fixation dropped by 6 to 17% in absolute terms from the baseline value (p = 0.027). Absorbance was not affected in higher frequencies (p = 0.725). Stapedotomy changed the absorbance curve significantly compared to the normal condition with an increase of absolute absorbance values by 6 to 36% around 0.25-1 kHz (p-value <0.01). The crimping conditions did not differ from one another (p = 0.555).
CONCLUSION: WAI is not useful in distinguishing between tightly crimped, loosely crimped and uncrimped stapes prostheses following stapedotomy.
PMID: 27534272 [PubMed - as supplied by publisher]
Wideband acoustic immittance measurements in assessing crimping status following stapedotomy: A temporal bone study.
Int J Audiol. 2016 Aug 18;:1-7
Authors: Wegner I, Shahnaz N, Grolman W, Bance ML
Abstract
OBJECTIVE: To ascertain if wideband acoustic immitance (WAI) measurements are useful in assessing crimping status following stapedotomy.
DESIGN: WAI measurements were obtained using the Mimosa Acoustics HearID system. Wideband chirp sound stimuli and a set of tone stimuli for nine frequencies between 0.2 and 6 kHz were used at 60 dB SPL. Five sets of measurements were performed on each temporal bone: mobile stapes, stapes fixation and stapedotomy followed by insertion of a tightly crimped, a loosely crimped and an uncrimped prosthesis.
STUDY SAMPLE: Eight fresh-frozen temporal bones were harvested from human cadaveric donors.
RESULTS: At lower frequencies, up to 1 kHz, stapes fixation decreased absorbance. Compared to the baseline absorbance, absorbance with stapes fixation dropped by 6 to 17% in absolute terms from the baseline value (p = 0.027). Absorbance was not affected in higher frequencies (p = 0.725). Stapedotomy changed the absorbance curve significantly compared to the normal condition with an increase of absolute absorbance values by 6 to 36% around 0.25-1 kHz (p-value <0.01). The crimping conditions did not differ from one another (p = 0.555).
CONCLUSION: WAI is not useful in distinguishing between tightly crimped, loosely crimped and uncrimped stapes prostheses following stapedotomy.
PMID: 27534272 [PubMed - as supplied by publisher]
Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss.
J Hum Genet. 2016 Aug 18;
Authors: Cai XZ, Li Y, Xia L, Peng Y, He CF, Jiang L, Feng Y, Xia K, Liu XZ, Mei LY, Hu ZM
Abstract
Hearing impairment, or deafness (in its most severe form), is one of the most common human sensory disorders. There have been several reports of autosomal dominant mutations in the POU4F3 gene, which is associated with non-syndromic hearing loss. In this study, we identified a novel heterozygous mutation (c.602delT, p.L201fs) in the gene POU4F3 by taking advantage of whole-exome sequencing, which was validated by Sanger sequencing and completely co-segregated within a large hearing impaired Chinese family. We have focused on this pedigree since 2002, and we have mapped a deafness locus named DFNA42 (which has been renamed DFNA52, OMIM entry 607683) via a genome-wide scan. Furthermore, we analyzed this mutational variant and found that it was located at the beginning of the first functional domain of POU4F3, which could theoretically impair the function of POU4F3. We have identified a novel frameshift mutation in the POU4F3 gene. Further functional studies of variants of this specific gene are needed to illustrate the pathogenic mechanism(s) that underlie hearing impairment.Journal of Human Genetics advance online publication, 18 August 2016; doi:10.1038/jhg.2016.102.
PMID: 27535032 [PubMed - as supplied by publisher]
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A novel loss-of-function mutation of GATA3 (p.R299Q) in a Japanese family with Hypoparathyroidism, Deafness, and Renal Dysplasia (HDR) syndrome.
BMC Endocr Disord. 2015;15:66
Authors: Okawa T, Yoshida M, Usui T, Kudou T, Iwasaki Y, Fukuoka K, Takahashi N, Uehara Y, Oiso Y
Abstract
BACKGROUND: Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder caused by mutations in the zinc finger transcription factor gene, GATA3. GATA3 has 2 zinc finger domains, which play an important role in the increase in target gene transcription activity.
CASE PRESENTATION: A 50-year-old woman and her 27-year-old daughter were followed up because of hypoparathyroidism. They had bilateral sensorineural deafness. Abdominal computed tomography scanning revealed renal dysplasia in the mother, but no renal anomaly in the daughter. Direct sequencing of GATA3 gene revealed a novel heterozygous missense mutation at codon 299 (p.R299Q) in exon 4. This mutation is located at the junction between the 2 zinc fingers. The structure prediction showed that it caused a conformation change in this junction area, affecting the spatial position of the zinc fingers. Additionally, a more marked conformation change was observed in the N-terminal zinc finger region compared to that in the C-terminal region. Functional analysis of this mutant protein using an in vitro luciferase reporter assay system confirmed that the mutation abolished the enhancing effects of wild-type GATA3 on the promoter activity of the consensus GATA responsive element and that of human PTH gene.
CONCLUSION: We identified a novel R299Q mutation in GATA3 in a Japanese family with HDR syndrome. We confirmed that R299Q is a loss-of-function mutation, due to the extensive conformational change in the zinc fingers of GATA3.
PMID: 26514990 [PubMed - indexed for MEDLINE]
