Andre Sadeghi

Spectrum of USH2A Mutations in Scandinavian Patients with Usher Syndrome Type II

Usher syndrome type II (USH2) is an autosomal recessive disorder, characterised by moderate to severe high‐frequency hearing impairment, normal balance function and progressive visual impairment due to retinitis pigmentosa. Usher syndrome type IIa, the most common subtype, is defined by mutations in the USH2A gene encoding a short and a recently discovered long usherin isoform comprising 21 and 73 exons, respectively. More than 120 different disease‐causing mutations have been reported, however, most of the previous reports concern mutations restricted to exons 1–21 of the USH2A gene. To explore the spectrum of USH2A disease‐causing mutations among Scandinavian USH2 cases, patients from 118 unrelated families of which 27 previously had been found to carry mutations in exons 1–21 were subjected to extensive DNA sequence analysis of the full size USH2A gene. Altogether, 122 USH2A DNA sequence alterations were identified of which 57 were predicted to be disease‐causing, 7 were considered to be of uncertain pathogenicity and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations 31 were located in exons 22–73, specific to the long isoform. USH2A mutations were identified in 89/118 (75.4%) families. In 79/89 (88.8%) of these families two pathogenic mutations were identified whereas in 10/89 (11.2%) families the second mutation remained unidentified. In 5/118 (4.2%) families the USH phenotype could be explained by mutations in the USH3A gene. The results presented here provide a comprehensive picture of the genetic aetiology of Usher syndrome type IIA in Scandinavia as it is known to date.

Baha solutions for patients with severe mixed hearing loss.

Abstract Patients with a mixed hearing loss present special challenges. The amplification demands of mixed hearing loss can drive powerful digital hearing aids to their limits and introduce distortion through saturation. Conversely, the Baha® System effectively bypasses the conductive component and focuses on compensating for the sensorineural component of the hearing loss. Ten patients with a mixed hearing loss participated in the present study. Results indicate that Baha provided significant benefits (p < 0.01) over conventional air conduction hearing instruments across the dimensions of audibility, speech understanding and sound quality. Given the increased output force of the latest Baha instruments, once the conductive component of a severe mixed hearing loss becomes greater than 30 dB, a Baha should be considered and evaluated on audiological grounds alone to provide optimal amplification. Copyright

Expressivity of hearing loss in cases with Usher syndrome type IIA

Abstract Objective: The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A. Design: DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations. Study sample: Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA. Results: Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations. Conclusions: Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.

Hearing Performance Benefits of a Programmable Power Baha ® Sound Processor with a Directional Microphone for Patients with a Mixed Hearing Loss

Objectives New signal processing technologies have recently become available for Baha® sound processors. These technologies have led to an increase in power and to the implementation of directional microphones. For any new technology, it is important to evaluate the degree of benefit under different listening situations. Methods Twenty wearers of the Baha osseointegrated hearing system participated in the investigation. The control sound processor was the Baha Intenso and the test sound processor was the Cochlear™ Baha® BP110power. Performance was evaluated in terms of free-field audibility with narrow band noise stimuli. Speech recognition of monosyllabic phonetically balanced (PB) words in quiet was performed at three intensity settings (50, 65, and 80 dB sound pressure level [SPL]) with materials presented at 0 degrees azimuth. Speech recognition of sentences in noise using the Hearing in Noise Test (HINT) in an adaptive framework was performed with speech from 0 degrees and noise held constant at 65 dB SPL from 180 degrees. Testing was performed in both the omni and directional microphone settings. Loudness growth was assessed in randomly presented 10 dB steps between 30 and 90 dB SPL to narrow band noise stimuli at 500 Hz and 3,000 Hz. Results The test sound processor had significantly improved high frequency audibility (3,000-8,000 Hz). Speech recognition of PB words in quiet at three different intensity levels (50, 65, and 80 dB SPL) indicated a significant difference in terms of level (P<0.0001) but not for sound processor type (P>0.05). Speech recognition of sentences in noise demonstrated a 2.5 dB signal-to-noise ratio (SNR) improvement in performance for the test sound processor. The directional microphone provided an additional 2.3 dB SNR improvement in speech recognition (P<0.0001). Loudness growth functions demonstrated similar performance, indicating that both sound processors had sufficient headroom and amplification for the required hearing loss. Conclusion The test sound processor demonstrated significant improvements in the most challenging listening situation (speech recognition in noise). The implementation of a directional microphone demonstrated a further potential improvement in hearing performance. Both the control and test sound processors demonstrated good performance in terms of audibility, word recognition in quiet and loudness growth.

Benefits of directional microphones and noise reduction circuits for improving Baha® hearing performance

Introduction Recently, implantable bone conduction systems (e.g. Baha, Cochlear Bone Anchored Solutions AB, Molnlykke, Sweden) have undergone a number of critical improvements with both sound processor and implant technology. A number of authors have reported on the improvement in speech understanding achievable from the latest Baha 3 system sound processors (Kompis and Pfiffner, 2010; Davison et al., 2009). Key to these improvements was the utilization of multiple channel non-linear sound processing technology in which the sound signal is processed across multiple frequency channels and the amplification is applied non-linearly to match the dynamic range of the Baha sound processor. Specifically, it has been found that directional microphones provide a hearing performance benefit for wearers of Baha (Oeding et al., 2010; Kompis et al., 2007). Lately, directional microphones have become both automatic and adaptive. Automatic in that the sound processor makes the decision when the microphone mode should be in omni or in directional mode. Adaptive in that the polar response of the microphones can be adapted to provide the optimum reduction in noise from behind the listener. These newer systems may provide new benefits to the patient and should be evaluated. Stenfelt (2007) reported, as the Baha is worn posterior to the ear canal, that the listener will actually hear better from behind than in front. Adjusting the prioritization of the two microphones balances the microphone response so that the listener’s sound scape is not distorted by the abutment position. In order to improve sound quality, noise reduction systems can be implemented that adjust the amplification based on the amount of noise present in each channel. Once noise becomes sufficiently loud to cause annoyance, the amount of amplification in that channel can be tempered to improve comfort. Therefore, the latest generation of Baha sound processors put into service a number of advanced signal processing technologies aimed to improve speech understanding and overall sound quality. However, questions have been raised whether these technical improvements will translate to a clinically relevant improvement in hearing performance. The purpose of this study is to investigate these systems and determine the degree of potential benefit.