Biomedical subjects

Guy Van Camp

Publications and source records attributed to Guy Van Camp.

At least 19 recordsLinked to original sources

PubMed2007

A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1.

Otosclerosis is a common form of hearing impairment among white adults with a prevalence of 0.3-0.4%. It is caused by abnormal bone homeostasis of the otic capsule that compromises free motion of the stapes in the oval window. Otosclerosis is in most patients a multifactorial disease, caused by both genetic and environmental factors. In some cases, the disease is inherited as a monogenic autosomal dominant trait, sometimes with reduced penetrance. However, families large enough for genetic linkage studies are extremely rare. To date, five loci (OTSC1-5) have been reported, but none of the responsible genes have been cloned yet. An additional locus, OTSC6, has been reported to the HUGO nomenclature committee but the relevant linkage study has not been published. In this study, a genome-wide linkage study was performed in a large Greek pedigree segregating autosomal dominant otosclerosis. A seventh locus, OTSC7, was localized on chromosome 6q13-16.1 with a multipoint LOD score of 7.5 in the 13.47 cM region defined by markers D6S1036 (centromeric) and D6S300 (telomeric). Linkage analysis of this new locus in 13 smaller Belgian and Dutch families has identified one family from The Netherlands in which allele segregation suggests linkage to this region. The overlap between the critical regions of these two families is a 1.06 Mb interval between the genetic markers D6S1036 (centromeric) and D6S406 (telomeric) on chromosome 6q13.

Chromosome Mapping↗

PubMed2006

Ozzy, a Jag1 vestibular mouse mutant, displays characteristics of Alagille syndrome.

The mouse mutant Ozzy, originating from an ENU-mutagenesis programme, displays a head bobbing phenotype. We report here that Ozzy mice show a clear deficit in vestibulo-ocular reflex (VOR). Micro-CT scanning of the inner ears showed narrowing and truncations of at least one of the semicircular canals and loss of the ampullae. Frequency-specific auditory-evoked brainstem response (ABR) tests revealed a slight threshold increase in the middle frequency range compared to wild-type littermates. Linkage analysis localised the gene in a 5.5-cM region on chromosome 2. Subsequently, a 499 T-->A missense mutation was identified in Jag1, leading to a substitution of an evolutionary conserved tryptophane (W167R). Mutations in the human homologue of Jag1 cause Alagille syndrome (AGS), an autosomal dominant disorder associated with liver, heart, eye and skeletal abnormalities, accompanied by a characteristic facies. In human patients, it occasionally affects other organ systems like the kidney or the inner ear. Liver disease is the main diagnostic factor for AGS. Ozzy mice showed significantly less intrahepatic bile ducts than wild-type littermates. Thirty-seven percent of Ozzy mice showed heart defects. No eye or vertebral abnormalities could be detected. In conclusion, Ozzy mice show two of the major and one minor characteristic of AGS.

Alagille Syndrome↗

PubMed2006

A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene.

Stickler syndrome is characterized by ophthalmic, articular, orofacial, and auditory manifestations. It has an autosomal dominant inheritance pattern and is caused by mutations in COL2A1, COL11A1, and COL11A2. We describe a family of Moroccan origin that consists of four children with Stickler syndrome, six unaffected children, and two unaffected parents who are distant relatives (fifth degree). All family members were clinically investigated for ear, nose, and throat; ophthalmologic; and radiological abnormalities. Four children showed symptoms characteristic of Stickler syndrome, including moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and epiphyseal dysplasia. We considered the COL9A1 gene, located on chromosome 6q13, to be a candidate gene on the basis of the structural association with collagen types II and XI and because of the high expression in the human inner ear indicated by cDNA microarray. Mutation analysis of the coding region of the COL9A1 gene showed a homozygous R295X mutation in the four affected children. The parents and four unaffected children were heterozygous carriers of the R295X mutation. Two unaffected children were homozygous for the wild-type allele. None of the family members except the homozygous R295X carriers had any signs of Stickler syndrome. Therefore, COL9A1 is the fourth identified gene that can cause Stickler syndrome. In contrast to the three previously reported Stickler syndrome-causing genes, this gene causes a form of Stickler syndrome with an autosomal recessive inheritance pattern. This finding will have a major impact on the genetic counseling of patients with Stickler syndrome and on the understanding of the pathophysiology of collagens. Mutation analysis of this gene is recommended in patients with Stickler syndrome with possible autosomal recessive inheritance.

Child↗

PubMed2006

Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy.

Auditory neuropathy is a particular type of hearing impairment in which neural transmission of the auditory signal is impaired, while cochlear outer hair cells remain functional. Here we report on DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is a paralog of DFNA5, a protein of unknown function also involved in deafness. By immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for the R183W variant identified in one DFNB59 family, show abnormal auditory brainstem responses indicative of neuronal dysfunction along the auditory pathway. Unlike previously described sensorineural deafness genes, all of which underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in nonsyndromic deafness due to a neuronal defect.

Amino Acid Sequence↗

PubMed2006

Doppler myocardial imaging in adult male rats: reference values and reproducibility of velocity and deformation parameters.

AIM: Limited data are available about the use of Doppler myocardial imaging (DMI) in small animals. We intend to provide reference values for velocity, strain and strain rate in a large group of healthy rats and studied the reproducibility and repeatability of these parameters. METHODS AND RESULTS: A total of 33 male Wistar rats (503+/-41g) underwent baseline transthoracic echocardiography with DMI of the anterior and inferior wall in a short-axis view using a 13MHz linear probe. Adequate tissue Doppler measurements could be obtained in 30 rats. On average 10+/-4 consecutive cycles were studied in post-processing using dedicated software (SPEQLE). Mean radial peak systolic velocity, strain and strain rate were respectively -0.8+/-0.3cm/s, 38+/-8% and 9.1+/-2.0/s in the anterior wall and 3.1+/-0.6cm/s, 49+/-10% and 13.7+/-3.7/s in the inferior wall. The reproducibility and repeatability of the DMI measurements assessed in 10 rats was good. CONCLUSION: DMI is feasible and reproducible in healthy rats. Establishing reference values opens new perspectives towards the use of strain and strain rate imaging in small rodents in the assessment of myocardial diseases.

Animals↗

PubMed2006

The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is one of the most important occupational diseases and, after presbyacusis, the most frequent cause of hearing loss. NIHL is a complex disease caused by an interaction between environmental and genetic factors. The various environmental factors involved in NIHL have been relatively extensively studied. On the other hand, little research has been performed on the genetic factors responsible for NIHL. To test whether the variation in genes involved in coupling of cells and potassium recycling in the inner ear might partly explain the variability in susceptibility to noise, we performed a case-control association study using 35 SNPs selected in 10 candidate genes on a total of 218 samples selected from a population of 1,261 Swedish male noise-exposed workers. We have obtained significant differences between susceptible and resistant individuals for the allele, genotype, and haplotype frequencies for three SNPs of the KCNE1 gene, and for the allele frequencies for one SNP of KCNQ1 and one SNP of KCNQ4. Patch-clamp experiments in high K+-concentrations using a Chinese hamster ovary (CHO) cell model were performed to investigate the possibility that the KCNE1-p.85N variant (NT_011512.10:g.21483550G>A; NP_00210.2:p.Asp85Asn) was causative for high noise susceptibility. The normalized current density generated by KCNQ1/KCNE1-p.85N channels, thus containing the susceptibility variant, differed significantly from that from wild-type channels. Furthermore, the midpoint potential of KCNQ1/KCNE1-p.85N channels (i.e., the voltage at which 50% of the channels are open) differed from that of wild-type channels. Further genetic and physiological studies will be necessary to confirm these findings.

Adult↗

PubMed2006

The phenotype of the first otosclerosis family linked to OTSC5.

OBJECTIVE: To report the audiometric and radiologic findings in the first otosclerosis family linked to OTSC5. STUDY DESIGN: A clinical investigation of a family linked to OTSC5, including analyses of audiometric data and of high-resolution computed tomography (CT) images of the temporal bones from genetically affected family members. SETTING: Tertiary referral center. PATIENTS: Family members from a four-generation pedigree with otosclerosis segregating as an autosomal dominant trait. MAIN OUTCOME MEASURE(S): Pre-surgery pure tone audiometric data. Classification of otosclerotic foci on high-resolution spiral CT images of the temporal bones of genetically affected individuals. RESULTS: Audiometric data showed a considerable degree of phenotypic variability. Cross-sectional regression analysis did not disclose any clear age dependence of threshold-related data. Systematic differences between mean parameter values relating to the thresholds in the best or the worst ear were found. High-resolution CT images revealed a fenestral otosclerotic focus in seven of nine (78%) clinically affected individuals and cochlear foci in one of these seven patients. CONCLUSION: The phenotype of OTSC5 seems to be variable. Additional long-term audiometric data are needed to construct age-related typical audiograms, which may also facilitate the comparison between phenotypes of the different otosclerosis loci. The detection rate of otospongiotic foci in our study group is similar or lower compared with previous reports on CT data in consecutive otosclerosis patients who had stapes replacing surgery.

Adult↗

PubMed2006

Audiometric analyses confirm a cochlear component, disproportional to age, in stapedial otosclerosis.

OBJECTIVE: To report the preoperative audiometric profile of surgically confirmed otosclerosis. STUDY DESIGN: Retrospective, multicenter study. SETTING: Four tertiary referral centers. PATIENTS: One thousand sixty-four surgically confirmed patients with otosclerosis. INTERVENTIONS: Therapeutic ear surgery for hearing improvement. MAIN OUTCOME MEASURES: Preoperative audiometric air conduction (AC) and bone conduction (BC) hearing thresholds were obtained retrospectively for 1064 patients with otosclerosis. A cross-sectional multiple linear regression analysis was performed on audiometric data of affected ears. Influences of age and sex were analyzed and age-related typical audiograms were created. Bone conduction thresholds were corrected for Carhart effect and presbyacusis; in addition, we tested to see if separate cochlear otosclerosis component existed. Corrected thresholds were than analyzed separately for progression of cochlear otosclerosis. RESULTS: The study population consisted of 35% men and 65% women (mean age, 44 yr). The mean pure-tone average at 0.5, 1, and 2 kHz was 57 dB hearing level. Multiple linear regression analysis showed significant progression for all measured AC and BC thresholds. The average annual threshold deterioration for AC was 0.45 dB/yr and the annual threshold deterioration for BC was 0.37 dB/yr. The average annual gap expansion was 0.08 dB/year. The corrected BC thresholds for Carhart effect and presbyacusis remained significantly different from zero, but only showed progression at 2 kHz. CONCLUSION: The preoperative audiological profile of otosclerosis is described. There is a significant sensorineural component in patients with otosclerosis planned for stapedotomy, which is worse than age-related hearing loss by itself. Deterioration rates of AC and BC thresholds have been reported, which can be helpful in clinical practice and might also guide the characterization of allegedly different phenotypes for familial and sporadic otosclerosis.

Adult↗

PubMed2005

Prevalence of mechanical dyssynchrony in patients with heart failure and preserved left ventricular function (a report from the Belgian Multicenter Registry on dyssynchrony).

The present study evaluated the prevalence of mechanical inter- and intraventricular dyssynchrony in patients with heart failure and preserved left ventricular (LV) ejection fraction (LVEF). We studied 138 patients with heart failure (age 67+/-11 years; 76% men); 60 patients had preserved LVEF (>40%). Using conventional Doppler echocardiography, an interventricular mechanical delay>or=40 ms was defined as interventricular dyssynchrony. Using pulse-wave tissue Doppler imaging, the time from the beginning of the QRS complex to onset of systolic motion was measured in 4 basal LV segments. A dispersion of >or=60 ms was defined as intraventricular dyssynchrony. The prevalence of inter- and intraventricular dyssynchrony was lower in patients with preserved LVEF than in those with reduced LVEF (17% vs 41%, p<0.01 for interventricular dyssynchrony, 18% vs 36%, p<0.01 for intraventricular dyssynchrony). However, patients with preserved LVEF and a QRS width>or=120 ms had higher values for the parameters for inter- and intraventricular dyssynchrony than patients with a QRS width<120 ms (interventricular mechanical delay 33+/-20 vs 20+/-16 ms, p<0.05; tissue Doppler imaging dispersion 42+/-26 vs 33+/-22 ms, p<0.05). In patients with a QRS width>or=120 ms, the prevalence of inter- and intraventricular dyssynchrony was comparable for patients with preserved and reduced LVEF (42% vs 55%, p=NS for interventricular dyssynchrony and 45% vs 46%, p=NS for intraventricular dyssynchrony). In conclusion, the prevalence of inter- and intraventricular dyssynchrony was low (17% and 18%, respectively) in patients with heart failure and preserved LVEF. However, in the presence of a QRS width of >or=120 ms, this prevalence increased to almost 50%, comparable to that for patients with heart failure and reduced LVEF and a QRS width of >or=120 ms.

Aged↗

PubMed2005

GJB2 mutations and degree of hearing loss: a multicenter study.

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.

Adolescent↗

PubMed2005

Monogenic nonsyndromic otosclerosis: audiological and linkage analysis in a large Greek pedigree.

OBJECTIVE: The aim of our study was to characterize the hearing impairment in a large multigenerational Greek family with autosomal dominant nonsyndromic otosclerosis and to perform genetic linkage analysis to known otosclerosis loci and collagen genes. In addition, we looked for mutations in the NOG gene to rule out congenital stapes ankylosis syndrome. METHODS: Audiological analysis of the affected persons was based on multiple linear regression (MLR) analysis and construction of age-related typical audiograms (ARTA). Genotyping of microsatellite DNA polymorphisms for known otosclerosis (OTSC) loci or collagen genes and linkage analysis using the MLINK computer program were performed. The coding region of the NOG gene was screened for mutations by direct DNA sequencing. RESULTS: The hearing loss in this family appears in childhood as conductive, but soon becomes mixed. Because the additional sensorineural component is progressive, this finally has lead to a pure sensorineural hearing loss in some family members, as the conductive component is masked. Audiological analysis showed an age-independent conductive component and a progressive frequency-specific sensorineural component. Linkage analysis excluded linkage to the four known otosclerosis loci (OTSC1, OTSC2, OTSC3, and OTSC5), as well as to the COL1A1 and COL1A2 genes. Mutation analysis of the coding region of the NOG gene did not reveal any disease causing mutation. CONCLUSIONS: This study represents the first description of a detailed audiological analysis in a large pedigree segregating otosclerosis as a monogenic autosomal dominant trait. Exclusion of the four known otosclerosis loci in this family shows that monogenic otosclerosis is a genetically heterogeneous disease involving at least five different genes. A mutation in the NOG gene is not the underlying molecular mechanism of the early onset otosclerosis segregating in this family.

Ankylosis↗

PubMed2005

Fine mapping of autosomal dominant nonsyndromic hearing impairment DFNA21 to chromosome 6p24.1-22.3.

Previously, the DFNA21 locus was positioned telomeric to the DFNA13 locus based on testing of candidate loci. One family member in this region did not carry the at risk haplotype, although he had the same nonspecific midfrequency hearing impairment as other affected family members. Hence, we performed a whole genome linkage scan excluding other regions of the genome and confirming the localization of DFNA21 to 6p22.3-24.1. The DFNA21 interval was determined to span 12.4 Mb (approximately 22 cM) and is delimited on the telomeric side by BV097155 and on the centromeric side by D6S1691. A maximum lod score of 3.51 (theta = 0.066), was calculated for marker D6S1721. The DFNA21 region does not overlap the adjacent DFNA31 and DFNA13 loci and contains 31 known genes. The coding regions and exon-intron boundaries of four candidate genes, SOX4, MYLIP, CAP2, and RPEL1, were sequenced, but no mutations were identified.

Chromosome Mapping↗

PubMed2005

A deafness mutation isolates a second role for the tectorial membrane in hearing.

Alpha-tectorin (encoded by Tecta) is a component of the tectorial membrane, an extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C mutation in Tecta, the tectorial membrane's matrix structure is disrupted, and its adhesion zone is reduced in thickness. These abnormalities do not seriously influence the tectorial membrane's known role in ensuring that cochlear feedback is optimal, because the sensitivity and frequency tuning of the mechanical responses of the cochlea are little changed. However, neural thresholds are elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen at the tip of the neural tuning curve. Thus, using Tecta(Y1870C/+) mice, we have genetically isolated a second major role for the tectorial membrane in hearing: it enables the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.

Acoustic Stimulation↗

PubMed2005

GJB2 (connexin 26) mutations are not a major cause of hearing loss in the Indonesian population.

Although hereditary hearing loss is a very heterogeneous disorder, variants in one gene, GJB2 (connexin 26), account for up to 50% of autosomal recessive nonsyndromal sensorineural hearing loss in most populations. This study investigates the contribution of GJB2 to autosomal recessive nonsyndromal hearing loss in the Indonesian population. We performed DNA sequence analysis in 120 patients with profound early childhood nonsyndromal hearing loss and in 100 control individuals and identified three novel variations resulting in amino acid substitutions (p.Gly4Asp, p.Thr5Ala, and p.Gly160Arg). Although we proved that p.Gly4Asp was not disease-causing, the pathological nature of p.Thr5Ala and p.Gly160Arg could not be determined. No recurrent disease-causing mutation could be detected in this Indonesian population. These findings are in contrast with the results obtained in other populations where GJB2 is a major cause of congenital recessive hearing loss.

Adolescent↗

PubMed2005

Global and regional parameters of dyssynchrony in ischemic and nonischemic cardiomyopathy.

In this study, color tissue Doppler imaging was used to assess global and regional mechanical dyssynchrony in patients with ischemic cardiomyopathy and those with idiopathic dilated cardiomyopathy. Potential differences in the area of latest mechanical activation could have practical implications regarding lead positioning and the success rate of biventricular pacemaker implantation.

Aged↗

PubMed2005

Mutation analysis of the GJB2 (connexin 26) gene in Egypt.

Fifty to eighty percent of autosomal recessive deafness is due to mutations in the GJB2 gene encoding connexin 26. Among Caucasians, the c.35delG mutation in this gene accounts for up to 30 to 70% of all cases with early childhood deafness. In this study, we present the analysis of the GJB2 gene in 159 Egyptians from 111 families with non-syndromic mild to profound hearing impairment. An additional family with Vohwinkel syndrome, a combination of hearing impairment and palmoplantar keratoderma with constriction of the digits, was also included. We used direct sequencing analysis to detect all possible coding GJB2 variants in this population. The presence of the g.1777179_2085947del mutation (hereafter called del(GJB6-D13S1830)) was also investigated as it was shown to be the second most common mutation causing non-syndromic prelingual hearing impairment in Spain. Sequencing analysis of one randomly chosen individual per family revealed that the c.35delG mutation was present in 24 out of 222 chromosomes (10.8%), making it the most frequent mutation in the GJB2 gene in Egypt. Five other mutations were already described previously [p.Thr8Met, p.Val37Ile, p.Val153Ile, c.333_334delAA, c.1-3172G>A (commonly designated as IVS1+1G>A)]. This study also revealed three other novel gene variants resulting in amino acid substitutions (p.Phe142del, p.Asp117His, p.Ala148Pro). In contrast with most populations, the del(GJB6-D13S1830) mutation upstream of the GJB2 gene was not present in this Egyptian population. A dominant mutation at a highly conserved residue, p.Gly130Val, was found in the family with Vohwinkel syndrome.

Adult↗

PubMed2005

Tissue Doppler imaging does not show infraclinical alteration of myocardial function after contrast echocardiography.

BACKGROUND: It has been previously suggested that simultaneous exposure of hearts to contrast and ultrasound can damage the myocardium and produce a transient decrease of the contractility in animals. Tissue Doppler imaging (TDI) is a useful tool to quantify the myocardial function with very high temporal resolution. AIM OF THE STUDY: The aim of the study was to test whether contrast echocardiography (CE) can cause alteration of the myocardial function by using tissue Doppler analysis. METHODS: Twenty-eight healthy patients (mean age: 44 +/- 22) underwent baseline echocardiography before and after 5 min of continuous intravenous infusion of Sonovue from the apical views, using an intermediate mechanical index (MI = 1). High frame rate images were acquired in tissue Doppler mode. Data were averaged over 3 cardiac cycles and analysed off-line before and after CE. RESULTS: There were no significant changes, before and after CE, in the peak systolic velocity (basal septum (BS): 6.2 +/- 2.2 vs 6.4 +/- 2.6; basal lateral (BL): 6.2 +/- 3.1 vs 6.4 +/- 3.3 cm/s), in the peak diastolic E velocity (BS: 5.4+/-1.8 vs 5.3+/-1.7; BL: 7.3+/-2.4 vs 7.7 +/- 3.2 cm/s), in the peak diastolic A velocity (BS: 6.3 +/- 1.9 vs 6.9 +/- 2.4; BL: 6.1 +/- 3.5 vs 6.2 +/- 2.5 cm/s), in the peak systolic strain (BS: 16 +/- 7 vs 17 +/- 7; BL: 12.6 +/- 5 vs 12.9 +/- 5%) and in peak systolic strain rate (BS: 1.3+/-0.6 vs 1.4+/-0.6; BL: 1.2+/-0.5 vs 1.21+/-0.51 1/sec). CONCLUSIONS: Our data suggest that CE does not cause alterations in the myocardial function as assessed by tissue Doppler imaging. CE, even with high MI settings, usually used for left ventricular opacification, can be safely performed.

Adult↗

PubMed2005

The influence of genetic variation in oxidative stress genes on human noise susceptibility.

Noise induced hearing loss (NIHL) is a complex disease caused by an interaction between genetic and environmental factors. Damage in the cochlea as a result of noise exposure appears to be mediated by reactive oxygen species (ROS). To investigate whether genetic variation in the human protective antioxidant system is associated with high or low susceptibility to NIHL, genetic polymorphisms derived from genes involved in the oxidative stress response were analysed in the 10% most susceptible and 10% most resistant extremes of 1200 Swedish noise-exposed workers. The genetic polymorphisms included 2 deletion polymorphisms for the GSTM1 and GSTT1 gene, and 14 SNPs derived from the CAT, SOD, GPX, GSR and GSTP1 genes. No significant differences were found between susceptible and resistant groups, providing no support for a major role of genetic variation of antioxidant enzymes in the susceptibility to NIHL.

Audiometry↗