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Objective: Unilateral sensorineural hearing loss (USNHL) is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood USNHL and analyze the associated audiological features., Study Design: Retrospective analysis of a prospectively recruited cohort., Setting: Tertiary referral center., Methods: We enrolled 38 children with USNHL between January 1, 2018, and December 31, 2021, and performed physical, audiological, imaging, and congenital cytomegalovirus (cCMV) examinations as well as genetic testing using next-generation sequencing (NGS) targeting 30 deafness genes. The audiological results were compared across different etiologies., Results: Causative genetic variants were identified in 8 (21.1%) patients, including 5 with GJB2 variants, 2 with PAX3 variants, and 1 with the EDNRB variant. GJB2 variants were found to be associated with mild-to-moderate USNHL in various audiogram configurations, whereas PAX3 and EDNRB variants were associated with profound USNHL in flat audiogram configurations. In addition, whole-genome sequencing and extended NGS targeting 213 deafness genes were performed in 2 multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and cCMV infection were observed in 9 and 2, respectively, patients without definite genetic diagnoses., Conclusion: Genetic underpinnings can contribute to approximately 20% of childhood USNHL, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of USNHL in children., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Pathogenic variants of the WFS1 gene can cause recessive-inherited Wolfram syndrome or dominant-inherited Wolfram-like syndrome with optic atrophy and hearing impairment. Using the Sendai virus delivery system, we generated induced pluripotent stem cells from the peripheral blood mononuclear cells of a female patient with the WFS1 pathogenic variant c.2051C > T (p.Ala684Val). The resulting induced pluripotent stem cells exhibited a normal karyotype and pluripotency, as confirmed using immunofluorescence staining, and differentiated into three germ layers in vivo. This cellular model provides a useful platform for investigating the pathogenic mechanisms of both blindness and deafness related to WFS1 variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Hearing impairment is one of the most common sensory disorders in children, and targeted next-generation sequencing (NGS)-based genetic examinations can assist in its prognostication and management. In 2020, we developed a simplified 30-gene NGS panel from the original 214-gene NGS version based on Taiwanese genetic epidemiology data to increase the accessibility of NGS-based examinations. In this study, we evaluated the diagnostic performance of the 30-gene NGS panel and compared it with that of the original 214-gene NGS panel in patient subgroups with different clinical features. Data on the clinical features, genetic etiologies, audiological profiles, and outcomes were collected from 350 patients who underwent NGS-based genetic examinations for idiopathic bilateral sensorineural hearing impairment between 2020 and 2022. The overall diagnostic yield was 52%, with slight differences in genetic etiology between patients with different degrees of hearing impairment and ages of onset. No significant difference was found in the diagnostic yields between the two panels, regardless of clinical features, except for a lower detection rate of the 30-gene panel in the late-onset group. For patients with negative genetic results, where the causative variant is undetectable on current NGS-based methods, part of the negative results may be due to genes not covered by the panel or yet to be identified. In such cases, the hearing prognosis varies and may decline over time, necessitating appropriate follow-up and consultation. In conclusion, genetic etiologies can serve as references for refining targeted NGS panels with satisfactory diagnostic performance.

Pathogenic variants of OPA1 have been associated with autosomal dominant optic atrophy (DOA), leading to optic, auditory, and other sensorineural neuropathies and myopathies. Using the Sendai virus delivery system, we generated induced pluripotent stem cells from the peripheral blood mononuclear cells of a female patient with the OPA1 pathogenic variant c.1468T>C (p.Cys490Arg). The resulting induced pluripotent stem cells exhibited a normal karyotype and pluripotency, as confirmed using immunofluorescence staining, and differentiated into three germ layers in vivo. This cellular model is a useful platform for investigating the pathogenic mechanisms of both blindness and deafness related to OPA1 variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Recessive variants of the SLC26A4 gene are an important cause of hereditary hearing impairment. Several transgenic mice with different Slc26a4 variants have been generated. However, none have recapitulated the auditory phenotypes in humans. Of the SLC26A4 variants identified thus far, the p.T721M variant is of interest, as it appears to confer a more severe pathogenicity than most of the other missense variants, but milder pathogenicity than non-sense and frameshift variants. Using a genotype-driven approach, we established a knock-in mouse model homozygous for p.T721M. To verify the pathogenicity of p.T721M, we generated mice with compound heterozygous variants by intercrossing Slc26a4 +/T721M mice with Slc26a4 919-2A>G/919-2A>G mice, which segregated the c.919-2A > G variant with abolished Slc26a4 function. We then performed serial audiological assessments, vestibular evaluations, and inner ear morphological studies. Surprisingly, both Slc26a4 T721M/T721M and Slc26a4 919-2A>G/T721M showed normal audiovestibular functions and inner ear morphology, indicating that p.T721M is non-pathogenic in mice and a single p.T721M allele is sufficient to maintain normal inner ear physiology. The evidence together with previous reports on mouse models with Slc26a4 p.C565Y and p.H723R variants, support our speculation that the absence of audiovestibular phenotypes in these mouse models could be attributed to different protein structures at the C-terminus of human and mouse pendrin., (© 2021. The Author(s).)

Gap junction protein beta 2 gene (GJB2) mutations are the most frequent cause of hereditary hearing impairment. The recessive c.235delC mutation in the GJB2 gene is the most common mutation causing severe to profound sensorineural hearing loss in the Asian population. The induced pluripotent stem cell (iPSC) line was generated using the integration-free Sendai virus method from peripheral blood mononuclear cells (PBMCs) of a hearing-impaired patient with homozygous GJB2 c.235delC mutation. This cell line may serve as a cellular model for studying the pathogenic mechanisms of deafness caused by GJB2 mutations., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of >5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI., Competing Interests: Declare conflicts of interest or state.

Purpose: The feasibility of genetic screening for deafness-causing mutations in newborns has been reported in several studies. The aim of this study was to investigate the long-term results in those who screened positive for deafness mutations; these results are crucial to determine the cost-effectiveness to justify population-wide genetic screening., Methods: We performed simultaneous hearing screening and genetic screening targeting four common deafness mutations (p.V37I and c.235delC of GJB2, c.919-2A>G of SLC26A4, and the mitochondrial m.1555A>G) in 5173 newborns at a tertiary hospital between 2009 and 2015. Serial audiometric results up to 6 years old were then analyzed in children with conclusive genotypes., Results: Newborn genetic screening identified 82 (1.6%) babies with conclusive genotypes, comprising 62 (1.2%) with GJB2 p.V37I/p.V37I, 16 (0.3%) with GJB2 p.V37I/c.235delC, and 4 (0.1%) with m.1555A>G. Of these, 46 (56.1%) passed hearing screening at birth. Long-term follow-up demonstrated progressive hearing loss in children with the GJB2 p.V37I/p.V37I and p.V37I/c.235delC genotypes; this hearing loss deteriorated by approximately 1 decibel hearing level (dBHL) per year., Conclusions: We delineated the longitudinal auditory features of the highly prevalent GJB2 p.V37I mutation on a general population basis and confirmed the utility of newborn genetic screening in identifying infants with late-onset or progressive hearing impairment undetectable by newborn hearing screening.Genet Med 19 1, 6-12.

Cochlear implantation is currently the treatment of choice for children with severe to profound hearing impairment. However, the outcomes with cochlear implants (CIs) vary significantly among recipients. The purpose of the present study is to identify the genetic determinants of poor CI outcomes. Twelve children with poor CI outcomes (the "cases") and 30 "matched controls" with good CI outcomes were subjected to comprehensive genetic analyses using massively parallel sequencing, which targeted 129 known deafness genes. Audiological features, imaging findings, and auditory/speech performance with CIs were then correlated to the genetic diagnoses. We identified genetic variants which are associated with poor CI outcomes in 7 (58%) of the 12 cases; 4 cases had bi-allelic PCDH15 pathogenic mutations and 3 cases were homozygous for the DFNB59 p.G292R variant. Mutations in the WFS1, GJB3, ESRRB, LRTOMT, MYO3A, and POU3F4 genes were detected in 7 (23%) of the 30 matched controls. The allele frequencies of PCDH15 and DFNB59 variants were significantly higher in the cases than in the matched controls (both P < 0.001). In the 7 CI recipients with PCDH15 or DFNB59 variants, otoacoustic emissions were absent in both ears, and imaging findings were normal in all 7 implanted ears. PCDH15 or DFNB59 variants are associated with poor CI performance, yet children with PCDH15 or DFNB59 variants might show clinical features indistinguishable from those of other typical pediatric CI recipients. Accordingly, genetic examination is indicated in all CI candidates before operation.

Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice.

To investigate the relationship between plasma reactive oxygen species (ROS) levels and severity of age-related hearing impairment in humans. We recruited 302 adult subjects aged 40-77 years with normal or symmetrical sensorineural hearing loss. The association of plasma ROS levels on pure tone average of low frequencies (PTA-low) and pure tone average of high frequencies (PTA-high) were analyzed. Luminol-dependent chemiluminescence signals, which reflect hydrogen peroxide (H(2)O(2)), hypochlorite (HOCl/OCl(-)) and hydroxyl radicals (•OH) levels, showed significant positive association with PTA-low and PTA-high after adjusting for age, gender, central obesity, systemic diseases, and health-related habits (smoking, drinking, antioxidant intake). Lucigenin-dependent chemiluminescence signals, which mainly reflect superoxide anion (O(2)•(-)) levels, showed significant positive association with PTA-low, but not with PTA-high after adjusting for other variables. We concluded that plasma ROS levels were associated with severity of age-related hearing impairment in humans. Various ROS may differently affect auditory dysfunctions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Obesity is an independent risk factor for age-related hearing impairment. Adiponectin is one of the major adipocytokines secreted by adipose tissue. The aim of our study was to examine whether there is an association between plasma adiponectin concentrations and hearing sensitivity in adults., Design and Methods: We recruited 954 adults aged 40-86 years, with normal or symmetrical sensorineural hearing loss and normal cognitive function. Backward stepwise multivariate linear regression was performed to assess the association between plasma adiponectin concentrations and hearing level Z-scores. Further, backward stepwise logistic regression analysis was performed to determine the risk of hearing impairment by plasma adiponectin concentration., Results: Adiponectin concentrations were lower, and waist circumference (WC) was higher in subjects with Z-high in the upper 50% of Z-high. Z-high (correlation coefficient: β = -0·02; standard error [SE] = 0·01; P = 0·003), but not Z-middle or Z-low, was significantly associated with plasma adiponectin concentrations after adjusting for WC, systemic diseases, smoking and alcohol consumption. The risk of hearing impairment for high frequencies, but not low or middle frequencies, decreased by 0·97-fold (odds ratio ± SE = 0·97 ± 0·02, P = 0·048, 95% confidence interval = 0·93-1·00) for every 1-unit increase in adiponectin concentration, after adjusting for age, gender, WC, systemic diseases, smoking and alcohol consumption., Conclusion: Plasma adiponectin may protect peripheral hearing function, particularly that related to high frequencies. Adiponectin may be a mediator of obesity-associated, age-related hearing impairment., (© 2011 Blackwell Publishing Ltd.)

Aminoglycoside ototoxicity is a common cause of drug-induced hearing loss. Toxicity is dose related, but some patients may still develop hearing loss even under safe dosage. Apart for genetic idiosyncrasy, indirect evidences imply that ischemia may increase the aminoglycoside ototoxic sensitivity because common clinical situations associated with cochlear ischemia such as noise, sepsis, and shock are known to augment the development of aminoglycoside ototoxicity. At present, a direct interaction of cochlear ischemia and aminoglycoside ototoxicity is still lacking. This study demonstrated a direct evidence of increased gentamicin (GM) ototoxic sensitivity in chronic guinea pig models of transient cochlear ischemia. No permanent auditory changes were observed after a single dose of GM (125 mg/kg) or after transient cochlear ischemia for 30 min. Persistent and significant auditory threshold shift was detected when GM was given after transient cochlear ischemia. Cochlear hair cells and spiral ganglion neurons are the major regions affected. Apoptosis contributes to hair cell death during acute interaction of ischemia and GM ototoxicity. Increased apoptotic cell death was also depicted when GM crossreacted with hypoxia in vitro, using cochlear cell lines. Generation of reactive oxygen species, loss of mitochondrial membrane potential, calcium release, and caspase-dependent apoptotic cell death were shown during the interaction of hypoxia and GM ototoxicity in vitro. This synergistic ototoxicity may be critical to aminoglycoside-induced hearing loss in clinical scenarios. The results should improve our understanding of the interacting mechanism and potential preventive strategy to aminoglycoside ototoxicity.

Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS.

Perturbation of cochlear microcirculation, that is, ischemia is a major cause of hearing impairment. Earlier studies examined the short-term (≤7 days) effect of cochlear ischemia. This study characterized the long-term (4 weeks) functional and morphological changes in adult guinea pig cochleae subject to transient ischemia by clamping the labyrinthine artery for 0.25-3 h. Notably, cochlear ischemia for over 1 h caused an increase of auditory brainstem response thresholds and loss of high-frequency hearing, basal-turn hair cells, and spiral ganglions. Auditory recovery may be possible after 30-min ischemia. The extent of the functional and morphological changes depended on the ischemia period, and the changes progressed in extent from the apical to the basal turn in an orderly fashion.

Recessive mutations in the SLC26A4 gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between SLC26A4 genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the SLC26A4 coding regions, the SLC26A4 promoter and the FOXI1 transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the SLC26A4 coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different SLC26A4 genotypes. Specifically, probands heterozygous for SLC26A4 mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.-2554G>A of SLC26A4) with possible pathological consequences, no definite mutation was detected after extensive screening in the SLC26A4 promoter and FOXI1. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of SLC26A4 by FOXI1. Meanwhile, exploration of undetected mutations in the SLC26A4 noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected SLC26A4 alleles of the c.919-2A>G heterozygotes, indicating that there might be no common and predominant mutations in the SLC26A4 introns.

Preimplantation genetic diagnosis (PGD) is used to analyze embryos genetically before their transfer into the uterus. For families with genetic diseases, PGD offers a chance to have an unaffected child, without facing termination of pregnancy. Although PGD has been performed for many monogenic disorders, such as cystic fibrosis and beta-thalassemia, the application of PGD to hereditary hearing impairment has not been explored. In the present study, we reported the development and application of PGD protocols to address enlarged vestibular aqueduct (EVA), which is a common type of hereditary hearing impairment associated with mutations in the SLC26A4 gene. The family requesting PGD had a history of EVA, segregating the SLC26A4 c.919-2A-->G mutation. In short, the PGD process was composed of two steps: the development of a single-cell testing protocol and clinical PGD cycles (i.e., selection and implantation of unaffected embryos using the single-cell testing protocol). First, protocols for genetic testing in a single cell were established for the c.919-2A-->G mutation using GenomiPhi technology and primer extension mini-sequencing. These protocols were validated on single lymphocytes collected from both parents and their affected child. Two clinical PGD cycles were then performed for the parents, with the second cycle successfully leading to a singleton pregnancy. The baby was homozygous for the wild-type SLC26A4 allele and revealed a normal audiological phenotype after birth. To our knowledge, this is the first report in the literature describing successful PGD in families with genetic hearing impairment. In our opinion, the application of PGD in the field of hereditary hearing impairment involves fewer ethical controversies than other novel applications of PGD and traditional indications for PGD for other monogenic diseases. Therefore, the approach demonstrated in the present study can also be used in a large number of families with other types of hereditary hearing impairment., (Copyright 2010 S. Karger AG, Basel.)

In Mandarin Chinese, tonal patterns are lexically meaningful. In a multi-talker environment, competing tones may create interference in addition to competing vowels and consonants. The present study measured Mandarin-speaking cochlear implant (CI) users' ability to recognize concurrent vowels, tones, and syllables in a concurrent-syllable recognition test. Concurrent syllables were constructed by summing either one Chinese syllable each from one male and one female talker or two syllables from the same male talker. Each talker produced 16 different syllables (4 vowels combined with 4 tones); all syllables were normalized to have the same overall duration and amplitude. Both single- and concurrent-syllable recognition were measured in 4 adolescent and 4 adult CI subjects, using their clinically assigned speech processors. The results showed no significant difference in performance between the adolescent and adult CI subjects. With single syllables, mean vowel recognition was 90% correct, while tone and syllable recognition were only 63% and 57% correct, respectively. With concurrent syllables, vowel, tone, and syllable recognition scores dropped by 40-60 percentage points. Concurrent-syllable performance was significantly correlated with single-syllable performance. Concurrent-vowel and syllable recognition were not significantly different between the same- and different-talker conditions, while concurrent-tone recognition was significantly better with the same-talker condition. Vowel and tone recognition were better when concurrent syllables contained the same vowels or tones, respectively. Across the different vowel pairs, tone recognition was less variable than vowel recognition; across the different tone pairs, vowel recognition was less variable than tone recognition. The present results suggest that interference between concurrent tones may contribute to Mandarin-speaking CI users' susceptibility to competing-talker backgrounds., (2009 Elsevier B.V.)

Background/purpose: Early hearing rehabilitation programs eventually require measurement of the hearing threshold cutoff values over the whole range of speech frequencies. With tone burst auditory brainstem responses, excellent agreement and correlation between evoked-potential and behavioral thresholds have been demonstrated by previous studies. This study investigated the effects of different ages and degrees of hearing loss on the agreement and correlation in a large series of infants and young children in Taiwan., Methods: Medical records were reviewed from a large series of 1281 infants and young children aged from 3 months to 3 years who had undergone diagnostic audiometry, including sound field audiometry and tone burst auditory brainstem response measurements. The effects of age and hearing loss on the agreement and correlation between two measured thresholds were studied., Results: Significant correlations (p < 0.001) were seen between the two measured thresholds across groups of different ages and different degrees of hearing loss greater than 20 dB HL. However, the degree of correlation deteriorated at lower degrees of hearing loss. Correlations for hearing thresholds less than 20 dB HL were not significant at 1000, 2000 and 4000 Hz., Conclusion: The evoked-potentials test, properly obtained and interpreted with respect to the effects of age and degree of hearing loss, may provide a very informative hearing threshold reference to help in behavioral audiometric evaluation in infants and young children with hearing loss.

Accurate epidemiological data on common deafness genes are essential to improve the efficiency and to reduce the cost of molecular diagnosis. They may depend on several factors, including a clear delineation of the source of patients being studied. In the present study, we hypothesize that patients with idiopathic sensorineural hearing loss recruited from different sources might reveal discrepancies in the epidemiological results of genetic screening, because patients from different sources might demonstrate distinct clinical or audiologic features and thus result in biased selection of subjects. To elucidate the relative importance of common deafness genes in Taiwanese and to verify our hypothesis, we conducted a prospective project screening mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with idiopathic bilateral sensorineural hearing loss, of which 325 families were recruited from hospitals and 95 from hearing rehabilitation facilities. Allele frequencies of common mutations in these three genes and distributions of the corresponding genotypes were then compared between the two groups. The allele frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele frequency of SLC26A4 mutations in the hospital group was significantly higher than that in the rehabilitation facility group (16.2 vs. 8.4%, chi(2)-test, p < 0.05), whereas no difference in the frequencies of GJB2 mutations and mitochondrial 12S rRNA mutations was found between the two groups. Distributions of probands classified by SLC26A4 genotypes were also different between the two groups (chi(2)-test, p < 0.05). Accordingly, a discrepancy in the genetic screening results might exist between different sources of idiopathic hearing-impaired patients. Further analysis of audiological results and construction of a logistic regression model showed that different audiological features, namely hearing levels and hearing loss patterns, might be responsible for the unequal distributions of mutations and probands between the hospital and rehabilitation facility groups., ((c) 2007 S. Karger AG, Basel)

Keywords: audit; cochlear implants; communication; diagnosis; genetics; hearing loss; inner ear; outcomes; sensorineural hearing loss EN audit cochlear implants communication diagnosis genetics hearing loss inner ear outcomes sensorineural hearing loss 341 346 6 02/17/22 20220301 NES 220301 Key Points LEOPARD syndrome is a rare hereditary disease characterised by several congenital defects in multiple organs, including sensorineural hearing impairment. The CI outcomes in LEOPARD syndrome patients are influenced by the I PTPN11 i genotypes because different I PTPN11 i mutations confer different pathogenicity on neurocognitive development. Audit, communication, diagnosis, genetics, inner ear, outcomes, sensorineural hearing loss, cochlear implants, hearing loss The authors attributed the unfavourable outcome to the patient's underlying cerebral palsy and late implantation.3 Nierop et al.4 reported another patient with LEOPARD syndrome caused by the I PTPN11 i p.Y279C mutation who received bilateral sequential CI at the ages of 1 years 4 months and 1 years 10 months. [Extracted from the article]

Objectives/Hypothesis: To explore the genetic characteristics of branchio-oto-renal (BOR) syndrome in an East Asian population. Study Design: Prospective clinical genetic study. Methods: Twelve families (total of 18 patients) who fulfilled the criteria for BOR syndrome were enrolled in this study. Mutation screening of the EYA1, SIX1, and SIX5 genes was performed by direct sequencing and quantitative polymerase chain reaction, and genotype-phenotype correlation was investigated. Results: Two novel EYA1 variants, c.466C>T (p.Q156X) and c.1735delG (p.D579fs), were identified in two multiplex families. The c.466C>T variant resulted in a truncated EYA1 protein, whereas the c.1735delG variant was predicted to encode an EYA1 protein with an abnormal C terminal. Neither variant was identified in a panel of 100 normal controls, and both were cosegregated with the BOR phenotype in the pedigrees, indicating that they were pathogenic mutations. No SIX1 and SIX5 mutations were detected in members of the remaining 10 families. Analysis of the genotype-phenotype correlation revealed a high phenotypic variability between and within BOR families. Conclusions: Two novel EYA1 mutations (c.466C>T and c.1735delG) were identified in two families with BOR syndrome. SIX1 and SIX5 mutations were not detected in the present study. Further investigation is warranted regarding the contribution of SIX1 and SIX5 mutations to BOR syndrome in East Asian populations. [ABSTRACT FROM AUTHOR]

Background/purpose: With respect to follow-up from newborn hearing screening, click evoked auditory brainstem response provides relatively accurate estimates of auditory thresholds at a broad frequency range between 1,000 Hz and 4,000 Hz. Further on the frequency-specific hearing evaluation, recent studies conclude that tone burst auditory brainstem response estimates the behavioral thresholds reasonably well. This study reports the preliminary data of tone burst auditory brainstem response measurements of infants and young children with normal hearing in Taiwan.Methods: Ninety-four infants and young children aged from 3 months to 3 years of age were recruited as they were eventually determined to have normal hearing after a series of tests. They underwent tone burst auditory brainstem response measurements at four selected frequencies. Statistical methods were applied to study the relationship among recorded variables.Results: The results indicated that the averaged tone burst auditory brainstem response thresholds of infants and young children with normal hearing in Taiwan are typically 10-20 dB nHL at 500, 1,000, 2,000, and 4,000 Hz, which is similar to the reported tone burst auditory brainstem response thresholds in adults with normal hearing. There was no statistically significant difference for the thresholds with regard to gender, laterality, and age distribution in this study.Conclusion: Based on the published research and our study, we suggest setting the normal criterion levels for infants and young children in Taiwan of the tone burst auditory brainstem response to air-conducted tones as 30 dB nHL for 500 and 1,000 Hz, and 25 dB nHL for 2,000 and 4,000 Hz. [ABSTRACT FROM AUTHOR]