Dataset Information

Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss.

ABSTRACT: The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion.

SUBMITTER: Sugiyama K

PROVIDER: S-EPMC6770988 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss.

Sugiyama Kenjiro K Moteki Hideaki H Kitajiri Shin-Ichiro SI Kitano Tomohiro T Nishio Shin-Ya SY Yamaguchi Tomomi T Wakui Keiko K Abe Satoko S Ozaki Akiko A Motegi Remi R Matsui Hirooki H Teraoka Masato M Kobayashi Yumiko Y Kosho Tomoki T Usami Shin-Ichi SI

Genes 20190916 9

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified C ...[more]

PMID: 31527525

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Project description:BackgroundTo date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.MethodsSubjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling.ResultsPathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive.ConclusionsTECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

Project description:The authors have demonstrated that the limited bandwidth associated with conventional hearing aid amplification prevents useful high-frequency speech information from being transmitted. The purpose of this study was to examine the efficacy of two popular frequency-lowering algorithms and one novel algorithm (spectral envelope decimation) in adults with mild to moderate sensorineural hearing loss and in normal-hearing controls.Participants listened monaurally through headphones to recordings of nine fricatives and affricates spoken by three women in a vowel-consonant context. Stimuli were mixed with speech-shaped noise at 10 dB SNR and recorded through a Widex Inteo IN-9 and a Phonak Naída UP V behind-the-ear (BTE) hearing aid. Frequency transposition (FT) is used in the Inteo and nonlinear frequency compression (NFC) used in the Naída. Both devices were programmed to lower frequencies above 4 kHz, but neither device could lower frequencies above 6 to 7 kHz. Each device was tested under four conditions: frequency lowering deactivated (FT-off and NFC-off), frequency lowering activated (FT and NFC), wideband (WB), and a fourth condition unique to each hearing aid. The WB condition was constructed by mixing recordings from the first condition with high-pass filtered versions of the source stimuli. For the Inteo, the fourth condition consisted of recordings made with the same settings as the first, but with the noise-reduction feature activated (FT-off). For the Naída, the fourth condition was the same as the first condition except that source stimuli were preprocessed by a novel frequency compression algorithm, spectral envelope decimation (SED), designed in MATLAB, which allowed for a more complete lowering of the 4 to 10 kHz input band. A follow-up experiment with NFC used Phonak's Naída SP V BTE, which could also lower a greater range of input frequencies.For normal-hearing and hearing-impaired listeners, performance with FT was significantly worse compared with that in the other conditions. Consistent with previous findings, performance for the hearing-impaired listeners in the WB condition was significantly better than in the FT-off condition. In addition, performance in the SED and WB conditions were both significantly better than in the NFC-off condition and the NFC condition with 6 kHz input bandwidth. There were no significant differences between SED and WB, indicating that improvements in fricative identification obtained by increasing bandwidth can also be obtained using this form of frequency compression. Significant differences between most conditions could be largely attributed to an increase or decrease in confusions for the phonemes /s/ and /z/. In the follow-up experiment, performance in the NFC condition with 10 kHz input bandwidth was significantly better than NFC-off, replicating the results obtained with SED. Furthermore, listeners who performed poorly with NFC-off tended to show the most improvement with NFC.Improvements in the identification of stimuli chosen to be sensitive to the effects of frequency lowering have been demonstrated using two forms of frequency compression (NFC and SED) in individuals with mild to moderate high-frequency sensorineural hearing loss. However, negative results caution against using FT for this population. Results also indicate that the advantage of an extended bandwidth as reported here and elsewhere applies to the input bandwidth for frequency compression (NFC/SED) when the start frequency is ?4 kHz.

Dataset Information

Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss.

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Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of <i>OTOA</i>-Associated Hearing Loss.

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