Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family

Kirschhofer, Karin; Kenyon, J. B.; Hoover, Denise M.; Franz, Peter; Weipoltshammer, Klara; Wachtler, F.; Kimberling, William J.

doi:10.1159/000015086

Cited by 42 publications

(31 citation statements)

References 21 publications

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“…The pattern is also different longitudinally along the length of the cochlear partition, in that higher levels of OHC loss are not found at the extreme base but in the middle region. This is consistent with the midfrequency hearing loss (the so-called "cookie bite" audiogram) that is commonly found in patients with many different types of TECTA mutations (Alasti et al 2008;Collin et al 2008;Govaerts et al 1998;Iwasaki et al 2002;Kirschhofer et al 1998;Moreno-Pelayo et al 2001;Plantinga et al 2006;Verhoeven et al 1998). Therefore, we consider it likely that the mechanisms of OHC loss described in this report are pertinent to the progressive hearing loss phenotype found in humans with TECTA mutations.…”

Section: Discussionsupporting

confidence: 88%

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Liu

Gao

Tao

et al. 2011

JARO

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The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Humans with an autosomal dominant C1509G mutation in alpha-tectorin, a protein constituent of the TM, are born with a partial hearing loss that worsens over time. The Tecta C1509/+ transgenic mouse with the same point mutation has partial hearing loss secondary to a shortened TM that only contacts the first row of OHCs. As well, Tecta C1509G/+ mice have increased expression of the OHC electromotility protein, prestin. We sought to determine whether these changes impact OHC survival. Distortion product otoacoustic emission thresholds in a quiet environment did not change to 6 months of age. However, noise exposure produced acute threshold shifts that fully recovered in Tecta +/+ mice but only partially recovered in Tecta C1509G/+ mice. While Tecta +/+ mice lost OHCs primarily at the base and within all three rows, Tecta C1509G/+ mice lost most of their OHCs in a more apical region of the cochlea and nearly completely within the first row. In order to estimate the impact of a shorter TM on the forces faced by the stereocilia within the first OHC row, both the wild type and the heterozygous conditions were simulated in a computational model. These analyses predicted that the shear force on the stereocilia is~50% higher in the heterozygous condition. We then measured electrically induced movements of the reticular lamina in situ and found that while they decreased to the noise floor in prestin null mice, they were increased by 4.58 dB in Tecta C1509G/+ mice compared to Tecta +/+ mice. The increased movements were associated with a fourfold increase in OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling the TM from some OHCs leads to partial hearing loss and places the remaining coupled OHCs at higher risk. Both the mechanics of the malformed TM and the increased prestin-related movements of the organ of Corti contribute to this higher risk profile.

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Section: Discussionsupporting

confidence: 88%

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Liu

Gao

Tao

et al. 2011

JARO

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“…In recent years, mouse models provided a lot of insight in the function of the tectorial membrane and the basis of these types of autosomal dominant midfrequency hearing impairment (Legan et al 1997(Legan et al , 2000(Legan et al , 2005McGuirt et al 1999). However, the exact mechanism of mutations altering protein interactions and thus influencing the mechanotransductional properties of the tectorial membrane remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Research on transgenic mice showed that the tectorial membrane facilitates the motion of the basilar membrane to optimally drive the inner hair cells (Legan et al 2005). The alpha-tectorin protein comprises three distinct modules: the entactin G1 domain, the zonadhesin (ZA) domain, and the zona pellucida (ZP) domain (Legan et al 1997). Mutations affecting the ZP domain are significantly associated with midfrequency hearing impairment, whereas mutations in the ZA domain are significantly associated with high frequency hearing impairment (Plantinga et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Audiological Evaluation of Affected Members from a Dutch DFNA8/12 (TECTA) Family

Plantinga

Cremers

Huygen

et al. 2006

JARO

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In DFNA8/12, an autosomal dominantly inherited type of nonsyndromic hearing impairment, the TECTA gene mutation causes a defect in the structure of the tectorial membrane in the inner ear. Because DFNA8/12 affects the tectorial membrane, patients with DFNA8/12 may show specific audiometric characteristics. In this study, five selected members of a Dutch DFNA8/12 family with a TECTA sensorineural hearing impairment were evaluated with pure-tone audiometry, loudness scaling, speech perception in quiet and noise, difference limen for frequency, acoustic reflexes, otoacoustic emissions, and gap detection. Four out of five subjects showed an elevation of pure-tone thresholds, acoustic reflex thresholds, and loudness discomfort levels. Loudness growth curves are parallel to those found in normalhearing individuals. Suprathreshold measures such as difference limen for frequency modulated pure tones, gap detection, and particularly speech perception in noise are within the normal range. Distortion otoacoustic emissions are present at the higher stimulus level. These results are similar to those previously obtained from a Dutch DFNA13 family with midfrequency sensorineural hearing impairment. It seems that a defect in the tectorial membrane results primarily in an attenuation of sound, whereas suprathreshold measures, such as otoacoustic emissions and speech perception in noise, are preserved rather well. The main effect of the defects is a shift in the operation point of the outer hair cells with near intact functioning at high levels. As most test results reflect those found in middle-ear conductive loss in both families, the sensorineural hearing impairment may be characterized as a cochlear conductive hearing impairment.

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“…Genotyping such traits succeeded within the decade around the past turn of the century.Hereditary mid-frequency hearing impairment has been diagnosed in families with DFNA8/12, DFNA13, DFNA21, DFNA31, DFNA44, DFNA49 [Brown et al, 1997;Ensink et al, 2001;Kirschhofer et al, 1998;Kunst et al, 2000;McGuirt et al, 1999;Moreno-Pelayo et al, 2003;Snoeckx et al, 2004;Van Camp et al, 1997;Verhoeven et al, 1997Verhoeven et al, , 1998] and more recently in some cases of DFNA15 [Pauw et al, 2008], as well as in a family that carries a mutation in the Wolfram syndrome type 1 gene (WFS1). The latter gene is involved in DFNA6/14/38 [Fujikawa et al, 2007] and in the Wolfram syndrome.…”

mentioning

confidence: 99%

“…Mutations in TECTA are known to cause the autosomal dominant type of non-syndromic hearing impairment DFNA8/12 [Govaerts et al, 1998;Verhoeven et al, 1998] that has been mapped to the chromosomal locus 11q22-24 [Verhoeven et al, 1997;Kirschhofer et al, 1998]. …”

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confidence: 99%

Flat Threshold and Mid-Frequency Hearing Impairment in a Dutch DFNA8/12 Family with a Novel Mutation in <i>TECTA</i>

et al. 2008

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A novel TECTA mutation (c.5331G>A) was identified affecting α-tectorin just N-terminally of the zona pellucida domain in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. The present mutation is clearly associated with a flat-threshold type of hearing impairment. Intriguingly, our results demonstrated that the present TECTA mutation had a significant protective effect against presbyacusis. Substantial protection against presbyacusis is a novel finding in a family with autosomal dominant hearing impairment.

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Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family

Cited by 42 publications

References 21 publications

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Audiological Evaluation of Affected Members from a Dutch DFNA8/12 (TECTA) Family

Flat Threshold and Mid-Frequency Hearing Impairment in a Dutch DFNA8/12 Family with a Novel Mutation in <i>TECTA</i>

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