Spatial Hearing Questionnaire : Psychometric Properties of Turkish Version and Correlations with Hearing Skills

Objective: Self-report questionnaire is informative to assess general hearing disability. The aims of this study were to investigate the reliability of Turkish version of spatial hearing questionnaire (SHQ) and to analyze the validity of the SHQ by the correlation with speech, spatial, and qualities of hearing questionnaire (SSQ) and Turkish matrix sentence test (TMST). Methods: The first part of the study was the psychometric properties of the SHQ with 192 participants (137 with normal hearing, 55 with hearing loss). In the second and main part of the study, we applied two questionnaires (SHQ and SSQ) and TMST to people other than those included in the first part of the study (88 participants with bilateral sensorineural hearing loss). We compared the results of these two questionnaires and the TMST with the speech discrimination (SD) scores. Results: Turkish spatial hearing questionnaire’s internal consistency was 0.94 and 0.97 for individuals with normal hearing and for individuals with hearing loss, respectively. Moderate, positive, statistically significant correlation was observed between the SHQ and SSQ (r = 0:606, p = 0:001 in individuals with hearing loss who do not wear any hearing aid, and r = 0:627, p = 0:001 in hearing aid users), and SHQ and SD (r = 0:561, p = 0:032 in hearing aid users). According to TMST, moderate, positive, statistically significant correlation was found between SSQ and adaptive TMST in individuals with hearing loss who do not wear any hearing aid (r = 0:330, p = 0:033 for S0N90 and r = 0:364, p = 0:018 for S0N270). Conclusions: Turkish SHQ is a valid and reliable questionnaire for assessing hearing functions. SHQ, SSQ, and TMST are clinically beneficial measuring tools in planning the process of hearing rehabilitation and follow-up

Transient evoked otoacoustic emissions and contralateral suppressions in children with auditory listening problems

Tokgoz Yilmaz, Suna/0000-0002-4656-099XWOS: 000273848100008PubMed: 19411150Objectives: Transient evoked otoacoustic emissions (TEOAEs) are reflections of cochlear energy produced during the processing of sound. The suppression effect identified as the decrease with the additional tone stimulator of the otoacoustic emission amplitude is use for assessing efferent auditory system function. The aim of this study is to investigate the contralateral suppression effect (CSE) of transient evoked otoacoustic emissions (TEOAEs) in children with auditory listening problems (ALPs) compared to normal hearing children. Method: The study group (Group 1) was consisted of 12 ALP children (8 males and 4 females), aged 5-10 years, and associated with receptive and expressive language delay. The control group was consisted of (Group 2) 12 children with normal hearing levels, matched according to gender and age of TEOAEs and CSE of TEOAEs were investigated at 1.0-4.0 kHz in both groups. Results: For right ear, at 1.0 and 3.0 kHz, TEOAE amplitudes of the ALP group were significantly lower than the control group. At 2.0. 4.0 and 5.0 kHz of the right ear and at 1.0-5.0 kHz of the left ear, TEOAE amplitudes were found as not different between ALP and control groups. Suppression values of the ALP group were significantly lower than the control group at 1.0-2.0 kHz of the right ear and at 2.0 kHz of the left ear. At the other frequencies, there was no significant difference between the suppression values of the ALP and control groups. Conclusion: Lower suppression values in ALP group at all frequencies (significant at 1.0-2.0 and 2.0 kHz in the right and left ears, respectively) showed that cochlear and cranial maturation of the ALP group may lower than the control group. Since the age profile in both group is similar, we thought that ages effect on this results is not important. Our results showed that children with ALP have auditory processing difficulties in noisy environment. For understanding the efferent auditory system, patients with auditory processing disorders may be evaluated by the help of background noise. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Evidence for genotype–phenotype correlation for OTOF mutations

The aim of this study is to evaluate the auditory phenotype in subjects with OTOF gene mutations to describe genotype–phenotype correlations. Twenty-two affected members from three families with homozygous OTOF mutations were included. Nine subjects were evaluated audiologically with otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex testing, auditory brain stem responses, and otoacoustic emission tests. Homozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive sensorineural hearing loss in four siblings in one family, while homozygous c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural hearing loss without AN/AD in four relatives in another family. Homozygous c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural hearing loss without AN/AD in one affected person in an additional family. The audiological phenotype associated with different OTOF mutations appears to be consistently different suggesting the presence of a genotype–phenotype correlation

Audiological findings in Noonan syndrome

The aim of this study was to evaluate audiologic properties of patients with Noonan syndrome and compare these findings with those of unaffected peers. The study included 17 children with Noonan syndrome and 20 typically developing children without Noonan syndrome. Pure tone and speech audiometry, immitancemetric measurement, otoacoustic emissions measurement and auditory brainstem response tests were applied to all (n = 37) children. Hearing thresholds of children with Noonan syndrome were higher (poorer) than those observed unaffected peers, while the hearing sensitivity of the both groups were normal limits (p = 0.013 for right, p = 0.031 for left ear). Transient evoked otoacoustic emissions amplitudes of the children with Noonan syndrome were lower than the children without Noonan syndrome (p = 0.005 for right, p = 0.002 for left ear). Middle ear pressures and auditory brainstem response values were within normal limits and there was no difference between the two groups (p > 0.05). General benefit of the present study is to characterize the audiologic findings of children with Noonan syndrome, which is beneficial in clinics evaluating children with Noonan syndrome

A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss

While the importance of tight junctions in hearing is well established, the role of Claudin 9 (CLDN9), a tight junction protein, in human hearing and deafness has not been explored. Through whole-genome sequencing, we identified a one base pair deletion (c.86delT) in CLDN9 , encoding a tight junction protein, in a consanguineous family from Turkey with autosomal recessive nonsyndromic hearing loss. Three affected members of the family had sensorineural hearing loss (SNHL) ranging from moderate to profound in severity. The variant is predicted to cause a frameshift and produce a truncated protein (p.Leu29ArgfsTer4) in this single-exon gene. It is absent in public databases as well as in over 1000 Turkish individuals, and co-segregates with SNHL in the family. Our in vitro studies demonstrate that the mutant protein does not localize to cell membrane as demonstrated for the wild type protein. Mice lacking Cldn9 have been shown to develop SNHL. We conclude that CLDN9 is essential for proper audition in humans and its disruption leads to SNHL in humans

Novel variant p.E269K confirms causative role of PLS1

Auditory reception relies on the perception of mechanical stimuli by stereocilia and its conversion to electrochemical signal. Mechanosensory stereocilia are abundant in actin, which provides them with structural conformity necessary for perception of auditory stimuli. Out of three major classes of actin‐bundling proteins, plastin 1 encoded by PLS1, is highly expressed in stereocilia and is necessary for their regular maintenance. A missense PLS1 variant associated with autosomal dominant hearing loss (HL) in a small family has recently been reported. Here, we present another PLS1 missense variant, c.805G > A (p.E269K), in a Turkish family with autosomal dominant non‐syndromic HL confirming the causative role of PLS1 mutations in HL. We propose that HL due to the p.E269K variant is from the loss of a stable PLS1‐ACTB interaction. Variant p.E269K in PLS1 causing hearing loss

Dysfunction of GRAP , encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss

We have identified a variant (c.311A>T; p.Gln104Leu) cosegregating with autosomal recessive nonsyndromic deafness in two unrelated families. encodes a member of the highly conserved growth factor receptor-bound protein 2 (GRB2)/Sem-5/drk family of proteins, which are involved in Ras signaling; however, the function of the growth factor receptor-bound protein 2 (GRB2)-related adaptor protein (GRAP) in the auditory system is not known. Here, we show that, in mouse, is expressed in the inner ear and the protein localizes to the neuronal fibers innervating cochlear and utricular auditory hair cells. Downstream of receptor kinase ( ), the homolog of human , is expressed in Johnston's organ (JO), the fly hearing organ, and the loss of in JO causes scolopidium abnormalities. mutant flies present deficits in negative geotaxis behavior, which can be suppressed by human wild-type but not mutant GRAP. Furthermore, drk specifically colocalizes with synapsin at synapses, suggesting a potential role of such adaptor proteins in regulating actin cytoskeleton dynamics in the nervous system. Our findings establish a causative link between mutation and nonsyndromic deafness and suggest a function of GRAP/drk in hearing

FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing

In a large consanguineous Turkish kindred with recessive nonsyndromic, prelingual, profound hearing loss, we identified in the gene FAM65B (MIM611410) a splice site mutation (c.102-1G>A) that perfectly cosegregates with the phenotype in the family. The mutation leads to exon skipping and deletion of 52-amino acid residues of a PX membrane localization domain. FAM65B is known to be involved in myotube formation and in regulation of cell adhesion, polarization, and migration. We show that wild-type Fam65b is expressed during embryonic and postnatal development stages in murine cochlea, and that the protein localizes to the plasma membranes of the stereocilia of inner and outer hair cells of the inner ear. The wild-type protein targets the plasma membrane, whereas the mutant protein accumulates in cytoplasmic inclusion bodies and does not reach the membrane. In zebrafish, knockdown of fam65b leads to significant reduction of numbers of saccular hair cells and neuromasts and to hearing loss. We conclude that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing

ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice

Hair cells of the inner ear, the mechanosensory receptors, convert sound waves into neural signals that are passed to the brain via the auditory nerve. Little is known about the molecular mechanisms that govern the development of hair cell-neuronal connections. We ascertained a family with autosomal recessive deafness associated with a common cavity inner ear malformation and auditory neuropathy. Via whole-exome sequencing, we identified a variant (c. 2207G> C, p. R736T) in ROR1 (receptor tyrosine kinase-like orphan receptor 1), cosegregating with deafness in the family and absent in ethnicity-matched controls. ROR1 is a tyrosine kinase-like receptor localized at the plasma membrane. At the cellular level, the mutation prevents the protein from reaching the cellular membrane. In the presence of WNT5A, a known ROR1 ligand, the mutated ROR1 fails to activate NF-kappa B. Ror1 is expressed in the inner ear during development at embryonic and postnatal stages. We demonstrate that Ror1 mutant mice are severely deaf, with preserved otoacoustic emissions. Anatomically, mutant mice display malformed cochleae. Axons of spiral ganglion neurons show fasciculation defects. Type I neurons show impaired synapses with inner hair cells, and type II neurons display aberrant projections through the cochlear sensory epithelium. We conclude that Ror1 is crucial for spiral ganglion neurons to innervate auditory hair cells. Impairment of ROR1 function largely affects development of the inner ear and hearing in humans and mice