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

Abstract

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.

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

“…However, because this change was not present in the controls, it cannot be ruled out that it has an effect on the phenotype of these patients or it may even act synergistically with the T1866M (c.5597C4T) mutation. The similar results with two changes in one family were reported by Plantinga 12 in 2006. The T1866M mutation that we detected in this study was previously reported in one family each in Korea, Spain and the USA.…”

“…In this study, all patients showed typical genotype-phenotype correlations of SNHL with TECTA mutation as previously described. 8,12,15 The family F818 in which the R1773X (c.5318C4T) mutation in the ZA domain was detected, showed high frequency hearing loss that was slowly progressive. The affected proband (Figure 1) noticed bilateral hearing impairment when she was around age 20, and her right hearing level was worse than the left because of cholesteatoma in her right ear.…”

“…Missense mutations affecting the ZP domain are associated with mid-frequency hearing impairment, whereas mutations in the ZA domain are associated with hearing impairment primarily affecting the high frequencies. 12 Phenotypes of hearing loss can range from mild to severe and have pre or postlingual onset. 8 In this study, (1) we examined the prevalence of hearing loss caused by TECTA mutations in Japanese ADSHNL and confirmed genotypephenotype correlation, and (2) examined the impact of three missense mutations in the ZP domain on the cellular distribution of a-tectorin, known to cause mid-frequency hearing impairment.…”

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

“…However, there is a difference in the nature of the impairment between the two groups of patients. In presbyacusis, the impairment implies sensorineural hearing loss, whereas in the present patients, it mainly implies intracochlear conductive hearing loss [Plantinga et al, 2007].…”

“…Vestibular function was not evaluated because the family members were not willing to undergo the tests. The affected family members also did not wish to undergo further hearing tests, such as acoustic reflex thresholds, loudness discomfort levels, distortion product otoacoustic emissions to test outer hair cell functionality, frequency-modulated pure tones to assess frequency discrimination and speech perception in noise, as described before [Plantinga et al, 2007].…”