Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Effectiveness of cochlear implantation in children with auditory neuropathy and cochlear nerve aplasia / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>The aim of this study is to assess of cochlear implantation in children with auditory neuropathy and cochlear nerve aplasia by using Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR).</p><p><b>METHODS</b>Twenty one children with cochlear implants participated in this study. They all received cochlear implant surgery at our hospital from January 2004 to October 2010. All children had hearing aid trial and hearing and speech rehabilitation before surgery at least three months.Nine children (7 male, 2 female) were diagnosed with auditory neuropathy, twelve (7 male, 5 female) with cochlear nerve aplasia. Twenty children (10 male, 10 female) with sensorineural hearing loss served as a control group. All the children received cochlear implant for more than six months. Forty two children with normal hearing served as another control group which were divided into three subgroups according to their age.Group A included 18 children aged under two yrs, group B consisted of 16 children aged from two to four yrs and group C comprised eight children aged above four yrs. CAP and SIR were used to evaluate among all the children and the scores were compared.</p><p><b>RESULTS</b>The CAP scores of children with auditory neuropathy, cochlear nerve aplasia, sensorial neural hearing loss and the three subgroups children with normal hearing were 4.44 ± 1.50, 4.83 ± 1.69, 4.55 ± 1.66, 5.22 ± 1.11, 6.75 ± 0.45 and 7.00 ± 0.00 respectively, and SIR scores were 2.66 ± 1.11, 2.33 ± 1.15, 2.40 ± 0.75, 2.56 ± 1.04, 4.12 ± 0.81 and 5.00 ± 0.00 respectively. There were significant differences among the six groups for CAP scores(χ(2) = 35.481, P < 0.001) and SIR scores(χ(2) = 40.549, P < 0.001).No significant differences for CAP and SIR scores were observed between children with auditory neuropathy/cochlear nerve aplasia and sensorial neural hearing loss as well as group A (P > 0.05 for each), and there were significant differences were shown between children with auditory neuropathy/cochlear nerve aplasia and group B as well as group C (P < 0.01 for each aplasia).</p><p><b>CONCLUSIONS</b>The auditory and speech capabilities of children with auditory neuropathy and cochlear nerve deficiency can can get benefits from cochlear implants as children with sensorineural hearing loss, however not achieve the level of those with normal hearing after cochlear implantation. The long term effects still need follow-up and evaluation.</p>

Audiology characteristics in newborns and infants who failed in the hearing screening by transiently evoked otoacoustic emissions: 89 cases study / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>The present study was to evaluate the audiological characteristics of infants with normal auditory brainstem response thresholds in click and abnormal transiently evoked otoacoustic emissions. Relationships between test results of distortion product otoacoustic emissions (DPOAE) and other hearing testing methods were also evaluated.</p><p><b>METHODS</b>The participants consisted of eighty-nine infants, with a total of 123 ears. All participants' TEOAE screening results were abnormal but diagnostic click ABR results were normal. The participants were classified into the following groups based on the test results from distortion product otoacoustic emissions: group A (normal all-frequency), group B (abnormal low-frequency), group C (abnormal high-frequency), and group D (abnormal all-frequency).</p><p><b>RESULTS</b>Obtained from these groups were compared to results of other hearing tests including the latency of ABR wave I, 40 Hz auditory event related potential (40 Hz AERP), 226 Hz and 1000 Hz tympanometry, and acoustic reflex. Results In six hearing tests in the 123 ears, seven ears (5.7%) were normal, while 116 ears (94.3%) were abnormal. No significantly differences were detected between boys (93.9%) and girls (95.1%), as well as between left (93.1%) and right ears (95.4%). The proportion of abnormal test results ranked as follows: 59 ears in group D (48.0%), 34 ears in group B (27.6%), 20 ears in group A (16.3%), and 10 ears in group C (8.2%). The highest abnormal rates in groups A, B and D were acoustic reflex, which were 40.0% for group A, 55.9% for group B and 66.1% for group D respectively. The highest abnormal rate in group C was the latency of ABR wave I (50.0%). Distribution of low-frequency hearing loss in each group was mainly mild. However, one ear in group B was moderate hearing loss, six ears in group D were moderate hearing loss, and one ear in group D was severe hearing loss.</p><p><b>CONCLUSIONS</b>The present study showed that, of which infants with normal thresholds of ABR failed the hearing screening, comprehensively audiology assessment is needed. And of which infants with normal DPOAE in full frequency or abnormal in high frequency region or low frequency region need to be followed up.</p>

Outcome of cochlear implantation in prelingual pediatric auditory neuropathy / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the electrophysiological results and rehabilitation outcome of two prelingually deafened pediatric cochlear implant patients with auditory neuropathy.</p><p><b>METHODS</b>Preoperative audiological evaluation, intra-postoperative electrically evoked auditory brainstem response (EABR) and neural response telemetry (NRT) record for the two cases were conducted in Beijing Tongren Hospital. A one year follow-up was performed. Data collected before and at 6,12-month intervals after implantation were compared with that from control pediatric cochlear implant patients matched for the same duration of implant use as this two cases.</p><p><b>RESULTS</b>The two children implanted had not had any postoperative medical or cochlear implant device complications. Intraoperative EABR and NRT were elicited in case 1 with unrepeatable waveforms. After 12 months of training, Case 1 had shown significant improvements in sound detection, speech perception abilities and communication skills, which was better than the control group, and the electrophysiological results became normal. Case 2 had also benefited from cochlear implantation, even though no recognizable NRT was found until he returned 12 month after the operation. CONTUSIONS: The desynchronization of auditory path had been changed after the electrical stimulation ongoing 12 months for children with auditory neuropathy. The two children had not had any complications postoperatively, and each child had shown improved listening and communication skills. Cochlear implantation could help patients with auditory neuropathy to improve their communication skill and go back to the main stream.</p>

Comparison of sensitivity of audiological tests to identify otitis media with effusion in newborn infants / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the sensitive factors which were used in routine audiological tests to find out otitis media with effusion (OME) in newborn infants.</p><p><b>METHODS</b>Subjects of this study were 48 infants, including 31 males and 17 females, who failed in the universal newborn hearing screening. The age ranged from 1.5 to 12 months with the average age of 4.3 months. All subjects accepted temporal bone CT and routine audiological assessments, including air-conduction and bone-conduction auditory brainstem response (ABR), 40 Hz-auditory event related potential (40 Hz-AERP), distortion-product otoacoustic emission (DPOAE), acoustic reflex, tympanometries using 226 Hz and 1000 Hz probe tone. Nine factors were statistically analyzed using Kappa test, Univariate chi(2) test and multivariate condition Logistic stepwise regression analysis, which included the results of acoustic immittance, the air-conduction and bone-conduction ABR thresholds, the difference between air-conduction and bone-conduction ABR thresholds, the latency of ABR wave I, duration between ABR wave I and V, 40 Hz-AERP thresholds, amplitudes and thresholds of DPOAE, and acoustic reflex thresholds (ART).</p><p><b>RESULTS</b>Seventy-seven ears were diagnosed with OME, and 19 ears were normal. CT scan of temporal bone was set as a comparative standard. Kappa test indicated that the results of tympanometry with 1000 Hz probe tone (Kappa = 0.745, P < 0.001), the air-conduction ABR threshold (Kappa = 0.453, P < 0.001), the latency of ABR wave I (Kappa = 0.430, P < 0.001), the threshold of 40 Hz-AERP (Kappa = 0.582, P < 0.001), and DPOAE (Kappa = 0.495, P < 0.001) had agreement with the results of temporal bone CT on evaluating the function of middle ear. Univariate analysis indicated that sensitive factors of middle ear function in newborn infants were tympanometry with 1000 Hz probe tone (P < 0.001), ART (P < 0.001), the air-conduction ABR threshold (P < 0.001), the difference between air-conduction and bone-conduction ABR thresholds (P < 0.001), the latency of ABR wave I (P < 0.001), the threshold of 40 Hz-AERP (P < 0.001) and DPOAE (P < 0.001). And multivariate conditional Logistic stepwise regression model showed that tympanometry with 1000 Hz probe tone (P < 0.001) and 40 Hz-AERP threshold (P = 0.004) can be substituted into Logistic stepwise regression equation.</p><p><b>CONCLUSIONS</b>Tympanometry with 1000 Hz probe tone and are sensitive factors to find out OME in newborn infants. The air conduction ABR threshold, ABR wave I latency, 40 Hz-AERP threshold and DPOAE could reflect the middle ear function of newborn infants effectively.</p>

Infants hearing screening in the coastal villages of Shandong province / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study how to perform the hearing screening on the infants in the rural area.</p><p><b>METHODS</b>Three thousand nine hundreds and twenty-two infants, about 84% of them from rural, were born in the People Hospital of LaiZhou City from January to December in 2004. The infants were performed fast hearing screening by transient evoked otoacoustic emission (TEOAE) after the birth in 2-7 days. The fail cases were checked again after 4-6 weeks, and then were diagnosed if they still failed after following-up.</p><p><b>RESULTS</b>The infants (3612/3922, 92.1%) have been checked by TEOAE, and the examination was free in the poverty cases. The rate passed on the first check was 69.96% (2527/3922), but 1085 infants failed (30.4%), while 310 infants have not been checked (7.9%). In the 1085 cases that should be rechecked, there was only 633 cases (58.34%) accepted the check on time, while 452 cases (41.66%) missed. In the 163 cases with high-risk infants in 2004, 114 infants (69.96%) were checked, but 49 infants (29.04%) were not checked. Fourteen cases failed in the recheck, and 11 of them were checked by ABR. Two cases were found to be moderate and severe hearing loss in binaural respectively and 4 cases with mild hearing loss in monaural while 3 cases were normal.</p><p><b>CONCLUSIONS</b>It is necessary and viable for the infants on hearing screening in the rural area It should be set up and perfected the model for infants on hearing screening in rural area as soon as possible; it should be free for the poor infants to make sure everyone enjoy the health care.</p>

Bioavailability and bioequivalence of erythromycin ethylsuccinate granules in healthy volunteers / 中国感染与化疗杂志

Objective To study the bioavailability and bioequivalence of erythromycin ethylsuccinate granules in healthy male volunteers.Methods In a randomized two-period crossover study,20 healthy male volunteers received single 500 mg test and reference formulations of erythromyein ethylsuccinate granules.The plasma concentrations of erythromycin were assayed by microbiological method.Results The parameters of test and reference preparations were as follows:T_(max)(0.86?0.22)and (0.80?0.13)h,C_(max)(2.13?0.64)and(2.16?0.61)mg/L,t_(1/2)(2.04?0.2)and(1.97?0.4)h,AUC_(0-t)(4.96?1.73)and(4.63?1.52)mg?h/L,respectively.There was no significant difference between the two preparations.The rela- tive bioavailahility of the test granules was(109.1?22.8)%.Conclusions The two preparations of erythromycin ethylsucci- nate granules are bioequivalent.

Analysis of the found age and way for children age 0 to 6 with hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the children with hearing loss from the age 0 to 6, and discuss the found age, found way and audiological characteristics.</p><p><b>METHODS</b>General information of found age and found way of 265 children, were investigated with self-made questionnaire and routine audiological evaluations, and then made statistical analysis.</p><p><b>RESULTS</b>The average (x +/- s) found age for the children with hearing loss was (23.21 +/- 10.02) months, and the first average coming age was (28.01 +/- 13.41) months. The found age of girls [(27.11 +/- 13.13) months] was 6.1 months later than the boys' [(21.03 +/- 12.32) months] and the countryside children [(28.27 +/- 11.09) months] later than the city's [(19.52 +/- 13.05) months] 8.65 months in the average found age. The found age of children who were found with speech disability was later than others. As the hearing loss degree of children went milder, the found age might later.</p><p><b>CONCLUSIONS</b>The popularization of knowledge in preventing from hearing loss must be strengthened. It is also necessary to popularize newborn hearing screening and early intervention while to enhance the parents' consciousness.</p>

Follow-up study for newborns and infants who failed hearing screening / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the audiological characteristics of newborns and infants who failed hearing screening.</p><p><b>METHODS</b>One hundred and six infants failed hearing screening received follow-up study with routine audiological evaluations (auditory brainstem response, distortion product otoacoustic emission, tympanometry and visual reinforcement audiometry).</p><p><b>RESULTS</b>Sixty-five infants (61.3%) of this group were normal hearing subjects and 39(36. 8% ) of the infants had hearing loss. Two cases (1.9%) received follow-up by phone. Fifteen cases (14.2%) with conductive hearing loss and 24 cases (22.6%) with sensorineural hearing loss. Thirteen (12.3%), 14 (13.2%), 6 (5.7%), and 6 (5.7%) cases were found to be mild, moderate, severe and profound hearing loss respectively. Diagnosis of hearing loss in the thirty-nine infants conducted a prevalence of 0.264% (39/14 785) of congenital hearing loss (both binaural and monaural). The hearing level of those cases with severe and profound hearing loss basically did not change, but that of cases with mild and moderate hearing loss changed.</p><p><b>CONCLUSIONS</b>Early identification and intervention of infants with severe and profound hearing loss by 6 months of age were successful. Infants with mild and moderate hearing loss should be followed up to six or eight months and received routine audiologic evaluations.</p>