Profound Hearing Impairment Research Articles

Hearing loss without overt metabolic acidosis in ATP6V1B1 deficient MRL mice, a new genetic model for non-syndromic deafness with enlarged vestibular aqueducts.

Mutations of the human ATP6V1B1 gene cause distal renal tubular acidosis (dRTA; OMIM #267300) often associated with sensorineural hearing impairment; however, mice with a knockout mutation of Atp6v1b1 were reported to exhibit a compensated acidosis and normal hearing. We discovered a new spontaneous mutation (vortex, symbol vtx) of Atp6v1b1 in an MRL/MpJ (MRL) colony of mice. In contrast to the reported phenotype of the knockout mouse, which was developed on a primarily C57BL/6 (B6) strain background, MRL-Atp6v1b1vtx/vtx mutant mice exhibit profound hearing impairment, which is associated with enlarged endolymphatic compartments of the inner ear. Mutant mice have alkaline urine but do not exhibit overt metabolic acidosis, a renal phenotype similar to that of the Atpbv1b1 knockout mouse. The abnormal inner ear phenotype of MRL- Atp6v1b1vtx/vtx mice was lost when the mutation was transferred onto the C57BL/6J (B6) background, indicating the influence of strain-specific genetic modifiers. To genetically map modifier loci in Atp6v1b1vtx/vtx mice, we analysed ABR thresholds of progeny from a backcross segregating MRL and B6 alleles. We found statistically significant linkage with a locus on Chr 13 that accounts for about 20% of the hearing threshold variation in the backcross mice. The important effect that genetic background has on the inner ear phenotype of Atp6v1b1 mutant mice provides insight into the hearing loss variability associated with dRTA caused by ATP6V1B1 mutations. Because MRL-Atp6v1b1vxt/vtx mice do not recapitulate the metabolic acidosis of dRTA patients, they provide a new genetic model for nonsyndromic deafness with enlarged vestibular aqueduct (EVA; OMIM #600791).

Cochlear Implants in Children and Adults

About 4000 patients receive a cochlear implant in Germany every year. Adults have become the main group for cochlear implantation candidacy.Elderly people with progressive and profound hearing loss experienced high communication restraints due to the limits of conventional hearing aids in the past. Nowadays cochlear implants can be offered as a well-established extension to the supply chain of hearing systems. The option of cochlear implantation for children with profound hearing impairment has led to a paradigm shift in hearing rehabilitation. However, there is still great variability in spoken language outcomes in CI children. These range from communicative and linguistic competencies similar to normal hearing children to clearly limited receptive and productive language skills. Besides age of implantation and the quality of previous auditory stimulation, there are additional factors that likely influence the outcome after cochlea implantation. Among them are the quality of caregivers' linguistic input and an intensive post-operative rehabilitation and intervention program. Ideally, children with CI are included into mainstream educational settings. Considering the high incidence of additional disabilities in children with hearing loss, it seems obvious that this goal cannot be achieved by all implanted children. Therefore, highly complex and individualized rehabilitation concepts are needed, which, in addition to oral language intervention programs, include total communication approaches as well.

Systematic review: Radiological and histological evidence of cochlear implant insertion trauma in adult patients

Introduction: Cochlear implantation (CI) has developed from its origins in the 1980s. Initially, CI was for profound bilateral hearing impairment. However, candidacy for CI have become more widespread in recent years with unilateral implantation and an emphasis on hearing preservation.Evidence supports full electrode insertion in an atraumatic fashion into the scala tympani (ST) provides optimal hearing outcomes. The main aim of this systematic review was to elucidate the degree of trauma associated with CI insertion.Methods: A systematic literature search was undertaken using PubMed Medline. A grading system described by Eshraghi was used to classify cochlear trauma. Both radiological and histological studies were included.Results: Twenty one papers were identified which were relevant to our search. In total, 653 implants were inserted and 115 (17.6%) showed evidence of trauma. The cochleas with trauma had basilar membrane elevation in 5.2%, ruptured in 5.2%, the electrode passed from the ST to the SV in 84.4% and there was grade 4 trauma in 5.2%. The studies used a variety of histological and radiological methods to assess for evidence of trauma in both cadaveric temporal bones and live recipients.Conclusions: Minimizing cochlear trauma during implant insertion is important to preserve residual hearing and optimize audiological performance. An overall 17.6% trauma rate suggests that CI insertion could be improved with more accurate and consistent electrode insertion such as in the form of robotic guidance. The correlation of cochlea trauma with post-operative hearing has yet to be determined.

Contributions of Nat Durlach to the field of haptics: Research on tactual communication of speech and manual sensing of mechanical properties

As a sensory scientist, Nat’s earliest contributions were through his theoretical and experimental work in the area of binaural hearing. Early in his career, however, he demonstrated an interest in comparative sensory processing as evidenced by a study to determine if the masking-level difference observed in audition would be found for stimulation on the skin (it was). Nat’s interest in the sense of touch continued through his research concerned with the use of the tactual sense as a substitute for hearing in the communication of speech and language for individuals with profound hearing impairment. This research encompassed studies with experienced deaf-blind users of natural methods of tactual communication (to establish an “existence proof” for the information-bearing capacity of the tactual sense) as well as research on methods for encoding and displaying acoustic signals for presentation through tactile aids. In addition, Nat also spearheaded efforts concerned with the development of haptic displays for use in virtual environment and teleoperator systems. His research in this area was concerned with advancements in knowledge regarding manual sensing and manipulation through a set of basic psychophysical studies. In this talk, we will summarize some of Nat’s important contributions in both of these areas.

Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea

Profound hearing impairment can be overcome by electrical stimulation (ES) of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Thus, SGN survival is critical for CI efficacy. Application of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce SGN degeneration following deafness. We tested a novel method for local, continuous GDNF-delivery in combination with ES via a CI. The encapsulated cell (EC) device contained a human ARPE-19 cell-line, genetically engineered for secretion of GDNF. In vitro, GDNF delivery was stable during ES delivered via a CI. In the chronic in vivo part, cats were systemically deafened and unilaterally implanted into the scala tympani with a CI and an EC device, which they wore for six months. The implantation of control devices (same cell-line not producing GDNF) had no negative effect on SGN survival. GDNF application without ES led to an unexpected reduction in SGN survival, however, the combination of GDNF with initial, short-term ES resulted in a significant protection of SGNs. A tight fibrous tissue formation in the scala tympani of the GDNF-only group is thought to be responsible for the increased SGN degeneration, due to mechanisms related to an aggravated foreign body response. Furthermore, the fibrotic encapsulation of the EC device led to cell death or cessation of GDNF release within the EC device during the six months in vivo. In both in vitro and in vivo, fibrosis was reduced by CI stimulation, enabling the neuroprotective effect of the combined treatment. Thus, fibrous tissue growth limits treatment possibilities with an EC device. For a stable and successful long-term neurotrophic treatment of the SGN via EC devices in human CI users, it would be necessary to make changes in the treatment approach (provision of anti-inflammatories), the EC device surface (reduced cell adhesion) and the ES (initiation prior to fibrosis formation).

SOX10 mutation causes Waardenburg syndrome associated with distinctive phenotypic features in an Iranian family: A clue for phenotype-directed genetic analysis

BackgroundWaardenburg syndrome (WS) is a neurocristopathy characterized by hearing impairment and pigmentary disturbances in hair, eyes, and skin. WS is clinically heterogeneous and can be subdivided into four major types (WS1–WS4) where WS4 or Shah–Waardenburg is diagnosed when WS2 is accompanied by Hirschsprung disease (HD). Mutations of SOX10, EDN3/EDNRB have been identified in association with WS4. This study was aimed to determine the pathogenic variant in an Iranian pedigree affected with WS4. MethodA two-generation pedigree with three affected members and considerable phenotypic heterogeneity was recruited. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung disease. The other two also presented characteristics of WS2 and complained of chronic constipation with normal anorectal reflex. Sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon 3 of SOX10 confirmed by a series of evidence to be pathogenic. It resulted in p.L141P at the protein level. Leucin 141 is located in Nuclear Export signal, HMG box of the protein. ConclusionThis study is the first report of a WS4 family in the Iranian population. The mutation is associated with distinctive phenotypic profile (association of anosmia and chronic constipation with SOX10 mutations) and could further improve diagnosis and counseling of WS in the Iranian population and can contribute to phenotype-directed genetic analysis.

Broadening the phenotype of DFNB28: Mutations in TRIOBP are associated with moderate, stable hereditary hearing impairment

DFNB28 is characterized by prelingual, severe to profound sensorineural hearing impairment (HI). It is associated with mutations in exon 6 and 7 of TRIOBP and has not been reported in the European population. Here, we describe two isolated cases of Dutch origin with congenital, moderate HI and compound heterozygous mutations in TRIOBP. Three of the mutations are novel, one nonsense mutation (c.5014G>T (p.Gly1672*)) and two frameshift mutations (c.2653del (p.Arg885Alafs*120) and c.3460_3461del (p.Leu1154Alafs*29)). The fourth mutation is the known c.3232dup (p.Arg1078Profs*6) mutation. Longitudinal audiometric analyses in one of the subjects revealed that HI was stable over a period of 15 years. Vestibular function was normal. Predicted effects of the mutations do not explain the relatively mild phenotype in the presented subjects, whereas location of the mutation might well contribute to the milder HI in one of the subjects. It is known that isoform classes TRIOBP-4 and TRIOBP-5 are important for stereocilia stability and rigidity. To our knowledge, p.Gly1672* is the first pathogenic variant identified in DFNB28 that does not affect isoform class TRIOBP-4. This suggests that a single TRIOBP copy to encode wildtype TRIOBP-4 is insufficient for normal hearing, and that at least one TRIOBP copy to encode TRIOBP-5 is indispensable for normal inner ear function. Furthermore, this study demonstrates that DFNB28 can be milder than reported so far and that mutations in TRIOBP are thus associated with a heterogeneous phenotype.

Novel Mutations and Mutation Combinations of TMPRSS3 Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment.

Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in the TMPRSS3 gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8). TMPRSS3 mutations can be classified as mild or severe, and the phenotype is dependent on the combination of TMPRSS3 mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milder TMPRSS3 mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations in TMPRSS3, one novel mutation c.36delC [p.(Phe13Serfs⁎12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs⁎12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs⁎12). We concluded that different combinations of TMPRSS3 mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family.

Severe to profound hearing impairment: factors associated with the use of hearing aids and cochlear implants and participation in extended audiological rehabilitation

Objective: The objective of this study is to determine whether various demographic variables are associated with hearing aid (HA) and cochlear implant (CI) use and participation in extended audiological rehabilitation among patients with severe to profound hearing loss (HL), and to compare the use of unilateral and bilateral HAs.Study design: Multiple logistic regression analyses were used to analyze general HA use, binaural HA use, CI use and participation in extended audiological rehabilitation. A total of 2297 adult patients from The Swedish Quality Register of Otorhinolaryngology with a PTA4 (0.5, 1, 2 and 4 kHz) ≥ 70 dB HL in the better ear were included.Results: The degree of HL was associated with HA and CI use and participation in extended audiological rehabilitation. The patients with at least a college degree were more likely to use bilateral HAs, have a CI and participate in audiological rehabilitation, compared with those with elementary school education. The sex distribution was evenly divided, but the men indicated a lower level of participation in extended audiological rehabilitation. No significant associations where found for sex and HA or CI use.Conclusion: The degree of HL was the strongest factor associated with the use of HAs, CI and extended audiological rehabilitation among the patients.

Fatores relacionados à qualidade de vida de pais de crianças com deficiência auditiva

Hearing loss among children, particularly those with severe and profound hearing impairment, has an effect on their communication and development, which in turn can have a significant impact on their parents. This study aimed to evaluate the quality of life of parents of children with hearing loss and identify the associated factors. A cross-sectional study was carried out involving parents of children that went through phonoaudiological therapy at a public university clinic in the city of São Paulo. The research instruments used were: the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-bref), the Social Support Questionnaire 6 (SSQ-6) and the General Health Questionnaire (GHQ-12). Inferential statistical analysis was performed using the Student's t-test. The study included 29 parents, 26 mothers and 3 fathers, of 27 children with severe and profound hearing impairment. The mean of the domain scores of the WHOQOL-bref, on a scale of 0-100, ranged between 40-60 and the overall score was 53. The best performance was achieved in the physical domain (60.3) and the worst in the environment domain (40.5). The main factor associated with all domains of the WHOQOL-bref, as well as overall score was being satisfied with social support.

Adult Cochlear Implant Users Are Able to Discriminate Basic Tonal Features in Musical Patterns: Evidence From Event-related Potentials.

Measurement of electrophysiological correlates of discrimination abilities of basic musical features in pre- and postlingually deafened adult cochlear implant (CI) users. Electroencephalographic study. Comparison between CI users and matched normal hearing controls. Thirty-six hearing impaired adults using a cochlear implant for 4 to 15 months. Profound hearing impairment was acquired either before (N = 12) or after language acquisition (N = 17). Seven patients suffered from a single-sided deafness. Presentation of auditory stimuli consisting of musical four tone standard patterns and deviant patterns varying with regard to tone pitch, timbre, intensity, and rhythm of two different degrees. Analysis of electrophysiological, event-related mismatch responses. Cochlear implant users elicited significant mismatch responses on most deviant features. Comparison to controls revealed significantly smaller mismatch negativity amplitudes. Except for one parameter (pitch) there were no reliable differences between pre- and postlingually deafened CI users. Despite a highly reduced complexity of neural auditory stimulation by the cochlear implant device in comparison to the physiological cochlear input, CI users exhibit cortical discriminatory responses to relatively subtle basic tonal alterations.

Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family

ObjectiveIdentification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. MethodsAfter excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. ResultsAn unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. ConclusionIdentification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.

Consanguinity Among Parents of Iranian Deaf Children

BackgroundIt seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran.ObjectivesThe aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation.MethodsThis study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population.ResultsSixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases.ConclusionsOur data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage.

Sequencing of exons 4, 5, 12 of COCH gene in patients with postlingual sensorineural hearing loss accompanied by vestibular lesion.

IntroductionMutations at the DFNA9 locus on chromosome 14q12 are the third most common form of DFNA hearing loss, which is clinically characterized by late onset (in adulthood) progressive sensorineural hearing loss accompanied by vestibular dysfunction. The aim of the study was to search for COCH gene mutations (P51S, V66G, G87W, G88E, V104del, I109N, W117R, A119T, M512T, C542Y) in patients with severe or profound sensorineural hearing loss accompanied by a vestibular lesion.Material and methodsThe study was based on a group of 30 patients. Qualification criteria comprised the presence of progressive postlingual, severe to profound sensorineural hearing loss with tinnitus, early age of sensorineural hearing loss onset, before the 40th year of life, and a positive family history of early onset hearing loss. All patients were diagnosed with peripheral vestibular lesions.ResultsThe authors did not find P51S, V66G, G87W, G88E, V104del, I109N, W117R, A119T, M512T, or C542Y mutations in the COCH gene in the tested group (no differences were found in the nucleotide sequences of exomes 4, 5 and 12 when compared to the published cDNA sequence of the COCH gene).ConclusionsNo cochlin mutations were found in the group of patients with severe to profound sensorineural hearing impairment accompanied by a vestibular lesion. The COCH gene needs further exploration and analysis of genotype-phenotype correlations.

Known-Groups and Concurrent Validity of the Mandarin Tone Identification Test (MTIT)

ObjectiveThe Mandarin Tone Identification Test (MTIT) is a new test designed to assess the tone identification abilities of children with hearing impairment (HI). Evidence for reliability and sensitivity has been reported. The present study aimed to evaluate the known-groups and concurrent validity of the MTIT.DesignThe MTIT and Mandarin Pediatric Speech Intelligibility test (MPSI) were administered in quiet and in noise conditions. The known-groups validity was evaluated by comparing the performance of the MTIT on children with two different levels of HI. The MPSI was included to evaluate the concurrent validity of the MTIT.Study sample81 children with HI were recruited in the present study. They were Mandarin-speaking children with profound HI (mean age = 9; 0, n = 41) and with moderate to severe HI (mean age = 8; 9, n = 40).ResultsScores on the MTIT differed between the two groups with different hearing levels suggesting good known-groups validity. A strong relationship between tone and sentence perception both in quiet and in noise provided preliminary evidence for concurrent validity.ConclusionsThe present study confirmed that the MTIT has good known-groups validity and provided preliminary evidence for concurrent validity. The MTIT could be used to evaluate tone identification ability in children with HI with confidence.

Acoustic characteristics of vowels produced by Greek intelligible speakers with profound hearing impairment II: The influence of stress and context

Purpose: The present paper examines the influence of stress and context on selected acoustic characteristics of vowels produced by six adult Greek intelligible speakers with profound hearing impairment and six speakers with normal hearing (three males and three females in each group).Method: F1, F2 and F3 formant frequencies and the duration of vowels are measured in words of the form /′pVCV/ with V = /i, ɛ, ɐ, ɔ, u/ and C = /p, t, k, s/. Variation in these parameters due to context and stress is reported for the two genders. A co-articulatory measure and three measures that examine the area of the vowel space and differences along the F1 and F2 axes are calculated.Result: The results show a reduction of the vowel space in the unstressed condition for both groups, while vowel duration was found to be significantly longer in this condition for the speakers with hearing impairment. In addition, smaller C-to-V carryover co-articulatory effects were found for the speakers with hearing impairment.Conclusion: Findings are discussed within the framework of perceptual and production constraints in hearing impairment and with reference to current models of co-articulation.

“Effects of Antisense Oligonucleotide Treatment on Photoreceptor Function in a mouse Model of Usher Syndrome”

Usher syndrome (USH) is the most common cause of inherited deaf‐blindness. Depending on the type (I, II, or III), hearing impairment and vestibular dysfunction can be variable, but all Usher patients exhibit a progressive loss of vision due to retinitis pigmentosa (RP). Usher syndrome type 1 (USH1) is responsible for 35 – 45% of all Usher cases and is characterized by severe to profound hearing impairment and vestibular dysfunction at birth, as well as, the development of RP in early adolescence. 6–8% of USH1 are caused by mutations in the USH1C gene, which encodes the protein Harmonin. Harmonin has been shown to play an important role in the development and function of auditory hair cells in the cochlea; however, its role in the retina is unknown. Our lab has produced a knock‐in mouse model containing the human USH1C c.216G>A splicing mutation (216A) responsible for USH1 in Acadian patients of south Louisiana. These mice have profound hearing impairment, vestibular dysfunction, loss of visual function and slow retinal degeneration similar to patients. Recently, antisense oligonucleotides (ASOs) targeting the 216A mutation in these mice have been shown to enhance correct Ush1c gene and Harmonin protein expression, and be efficacious in rescuing hearing and vestibular function when administered by intraperitoneal injection (systemic). However, only marginal improvement in visual function was observed; possibly due to an insufficient concentration of the ASO in the eye. The purpose of this study was to evaluate visual function after an intravitreal (local) ASO treatment.Rod and cone photoreceptor function was evaluated by scotopic and photopic electroretinogram (ERG) analysis, respectively, in ASO‐treated 216AA mutant and littermate control mice. An increase in scotopic a‐wave amplitude was observed within 3 months of ASO treatment in 216A mutant mice compared with control littermates, indicating an early improvement in rod function. This improvement was observed when the mice were treated at 1, 3 or 6 months of age, suggesting a large temporal window for successful intervention between adolescence and adulthood. An analysis of photopic ERGs showed no differences in untreated 216AA mutant and control littermates, suggesting cone function is not affected in early stages of disease. These data demonstrate the potential of ASOs for the treatment of retinitis pigmentosa associated with Usher syndrome.Support or Funding InformationThis research was supported by grant #1359140 through the National Science Foundation

Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss wereobserved. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2.

Acoustic characteristics of vowels produced by Greek intelligible speakers with profound hearing impairment I: Examination of vowel space

Purpose: The study examines F1, F2 and F3 formant frequencies of vowels produced by six Greek intelligible speakers with profound hearing impairment and six speakers with normal hearing (three male and three female in each group).Method: The formant frequencies are measured in words of the form /ʹpVCV/ where V = /i, , , , u/ and C = /p, t, k, s/. The study examines differences in formant frequencies between the two groups and as a function of gender. Three measures are calculated to examine the area of the vowel space and differences along the F1 and F2 axes between the groups and genders.Result: The results show that the vowel space produced by the speakers with hearing impairment is considerably reduced. Greater reduction was evident for F2 compared to F1. Restricted formant frequency ranges and relatively large variation along F1 and/or F2 for selected vowels resulted in overlap among vowel categories. F3 frequencies were systematically lower and showed greater variation for the speakers with hearing impairment.Conclusion: The paper discusses findings with reference to perceptual and production constraints affecting the speech of individuals with hearing impairment.

Tympanometric assessment among a select cohort of deaf students

Background: Children and young adults with profound hearing impairment and/or deafness are equally at risk of developing other ear diseases such as otitis media with effusion (OME) and/or middle ear infections. Otoscopic diagnosis of middle ear effusion is often problematic, and clinicians' skills in that regard are notably variable. The objective of this study is to present the tympanometric findings among hearing-impaired students from a group of special schools for the hearing impaired in Kaduna metropolis. Participants and Methods: This was a prospective cross-sectional study conducted for 4 months between February and May, 2014. Students aged 7-18 years attending Kaduna State Special Education School for the deaf, Katsina road, and Demonstration School for the Deaf, Kawo, Kaduna, were recruited for the study. An interviewer-based questionnaire was developed to capture the student's demographic characteristics and clinical information. This was followed by ear examination and tympanometric tests. The data were analyzed using Statistical Package for the Social Sciences software, version 16. Results: A total of 294 participants were recruited into the study group, and there were 173 males (58.8%) and 121 females (41.2%). The age of the participants ranged from 7 to 18 years. The mean age of the study group was 13.6 years with a standard deviation of ΁ 3.6 years. Forty-three (14.6%) of them had dull and retracted tympanic membranes while the rest had intact shiny tympanic membrane. Tympanometric test showed that 281 participants (89.5%) had type A tympanogram while types B and C accounted for 21 (7.1%) and 9 (3.1%), respectively. Among the 43 participants with dull and retracted tympanic membrane via otoscopic examination, 13 had type A tympanogram (normal) while the rest had middle ear disorders (type B and C tympanograms). Conclusion: Middle ear diseases such as OME and eustachian tube dysfunction were found among the study population. There is a need for the provision of regular awareness lecture and periodic ear examination to prevent, detect, and treat imminent otologic diseases.