Objective:To analyze the hearing phenotypes of p. V37I homozygote and compound heterozygote mutation in GJB2 gene, and to provide basis for genetic counseling. Methods:Fifty-three subjects with p. V37I homozygote and compound heterozygote mutation were recruited at Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital from January 2023 to March 2024. All subjects received universal newborn hearing screening（UNHS）, 23-site chip neonatal deafness genetic screening and audiological tests, including ABR, acoustic immittance, DPOAE, ASSR. The results of newborn hearing screening and hearing diagnosis were compared between homozygous mutation group of 30 cases and compound heterozygous mutation group of 23 cases. Results:In 53 cases, the overall refer rate of UNHS was 64.15%（34/53）, the refer rate of homozygous mutation group was 80.00%（24/30）, which was higher than that of compound heterozygous mutation group（43.48%, 10/23）, the difference between the two groups was statistically significant（P<0.05）. Three subjects with p. V37I compound heterozygous mutation had passed UNHS and diagnosed with unilateral mild hearing loss. The average age of diagnosis of 53 cases was （3.77±1.40） months, 25 cases with hearing loss accounted for 47.17%, including 13 cases with unilateral, 12 cases with bilateral, 28 cases with normal hearing accounted for 52.83%. There was no significant difference between homozygous mutation group（56.67%, 17/30） and compound heterozygous mutation group（34.78%, 8/23） in the proportion of confirmed hearing loss（P>0.05）. Among 37 ears of 25 patients with hearing loss, the proportion of mild, moderate and profound hearing loss were 70.27%（26/37）, 27.03%（10/37） and 2.70%（1/37）, respectively. The hearing loss degree of the homozygous mutation group and the compound heterozygous mutation group were mainly mild, accounting for 70.37%（19/27） and 70.00%（7/10） respectively. There was no significant difference between the two groups in the distribution of hearing loss degree（P>0.05）. Conclusion:The probability of hearing loss was 47.17% in infants of GJB2 gene p. V37I homozygote and compound heterozygote mutation, mainly mild hearing loss. There was no difference in the probability of hearing loss and the distribution of hearing loss degree between the two groups. Patients with p. V37I homozygous and compound heterozygous mutation currently diagnosed as normal hearing need continuous clinical follow-up.
Humans ; Connexin 26 ; Heterozygote ; Homozygote ; Female ; Phenotype ; Male ; Mutation ; Connexins/genetics* ; Infant ; Infant, Newborn ; Hearing Tests ; Neonatal Screening ; Deafness/genetics* ; Genetic Testing

Infant, Newborn ; Humans ; Hearing Tests ; Neonatal Screening ; China ; Hearing

OBJECTIVE: To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases. METHODS: A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). RESULTS: Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%). CONCLUSION Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.
Child ; Infant, Newborn ; Humans ; Female ; Prospective Studies ; Connexins/genetics* ; Connexin 26/genetics* ; Glucosephosphate Dehydrogenase Deficiency ; Mutation ; Sulfate Transporters/genetics* ; DNA Mutational Analysis ; Genetic Testing/methods* ; Deafness/genetics* ; Neonatal Screening/methods* ; Hearing Loss, Sensorineural/genetics* ; High-Throughput Nucleotide Sequencing ; Solute Carrier Family 22 Member 5/genetics*

OBJECTIVE: To analyze the clinical significance of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province. METHODS: Results of audiological examinations, including transient evoked otoacoustic emission and automatic discriminative auditory brainstem evoked potentials, for 6 723 newborns born in Yuncheng area from January 1, 2021 to December 31, 2021, were retrospectively analyzed. Those who failed one of the tests were considered to have failed the examination. A deafness-related gene testing kit was used to detect 15 hot spot variants of common deafness-associated genes in China including GJB2, SLC26A4, GJB3, and mtDNA12S rRNA. Neonates who had passed the audiological examinations and those who had not were compared using a chi-square test. RESULTS: Among the 6 723 neonates, 363 (5.40%) were found to carry variants. These have included 166 cases (2.47%) with GJB2 gene variants, 136 cases (2.03%) with SLC26A4 gene variants, 26 cases (0.39%) with mitochondrial 12S rRNA gene variants, and 33 cases (0.49%) with GJB3 gene variants. Among the 6 723 neonates, 267 had failed initial hearing screening, among which 244 had accepted a re-examination, for which 14 cases (5.73%) had failed again. This has yielded an approximate prevalence of hearing disorder of 0.21% (14/6 723). Among 230 newborns who had passed the re-examination, 10 (4.34%) were found to have carried a variant. By contrast, 4 out of the 14 neonates (28.57%) who had failed the re-examination had carried a variant, and there was a significant difference between the two groups (P < 0.05). CONCLUSION Genetic screening can provide an effective supplement to newborn hearing screening, and the combined screening can provide a best model for the prevention of hearing loss, which can enable early detection of deafness risks, targeted prevention measures, and genetic counseling to provide accurate prognosis for the newborns.
Infant, Newborn ; Humans ; Connexins/genetics* ; Retrospective Studies ; Deafness/genetics* ; Connexin 26/genetics* ; Neonatal Screening/methods* ; Mutation ; Genetic Testing/methods* ; China/epidemiology* ; Hearing ; DNA Mutational Analysis

OBJECTIVE: To analyze the results of concurrent hearing and deafness genetic screening and follow up of newborns. METHODS: In total 33 911 babies born to 5 designated hospitals in Nanshan District of Shenzhen city from October 2017 to December 2019 were included. All subjects underwent concurrent hearing and deafness genetic screening covering 21 variants of 4 genes including GJB2, SLC26A4, GJB3 and Mt12SrRNA. For those with positive results, Sanger sequencing was carried out for confirmation. RESULTS: 93.32% subjects passed the first-round hearing screening, and 87.01% passed the recheck testing. The overall detection rate was 4.18%. The detection rates for GJB2, SLC26A4, GJB3 and Mt12srRNA variants were 1.98%, 1.58%, 0.37% and 0.25%, respectively. 126 and 84 subjects were found with high risk for delayed-onset and drug-induced hearing loss, respectively. In addition, 4 and 5 subjects were found to harbor homozygous/compound heterozygous variants of the GJB2 and SLC26A4 genes, respectively. Concurrent screening showed that subjects (with heterozygous variants) who did not passed the two round hearing test were as follows: GJB2 with 6.75% in the first round and 2.61% in the second round testing, SLC26A4 (3.3%/1.2%), GJB3 (0.72%/0.14%) and 12SrRNA (0.36%/Nil), respectively. Moreover, the No-pass rate in the subjects with homozygous or compound variants in single gene, heterozygous variant in single gene, heterozygous variant in multiple genes, and homozygous variant in GJB3 gene were significantly higher than the subjects with negative results of genetic screening. CONCLUSION Concurrent newborn genetic screening can enhance the effectiveness of hearing screening and enable earlier identification and intervention for children with hearing impairment. Follow-up can improve the diagnostic rate for children who are positive for the concurrent screening. Nevertheless, genetic and hearing screening cannot replace the diagnostic testing. It is necessary to conduct comprehensive analysis for the results of genetic and hearing screening and radiological examinations. Sanger sequencing and next-generation sequencing are critical for ascertain the diagnosis.
China/epidemiology* ; DNA Mutational Analysis ; Deafness/genetics* ; Follow-Up Studies ; Genes/genetics* ; Genetic Testing/statistics & numerical data* ; Hearing/genetics* ; Hearing Tests/statistics & numerical data* ; Humans ; Infant, Newborn ; Mutation ; Neonatal Screening

OBJECTIVE: To detect common pathogenic variants associated with congenital deafness among neonates from Huizhou and surrounding areas and discuss its implications. METHODS: Thirteen hot-spot mutations in four most common pathogenic genes were screened among 20 934 neonates from March 2017 to December 2019. RESULTS: In total 760 neonates were found to carry common pathogenic variants (3.63%). Sixty two neonates have carried homozygous/compound heterozygous variants or homoplasmy/heteroplasmy mutations of mtDNA (0.29%). Further analysis of five abnormal cases revealed that 3 of them have carried compound heterozygous mutations of GJB2 gene, and 2 were due to compound heterozygous variants of the CDH23 gene. CONCLUSION Genetic testing has a great clinical significance for the prevention and reduction of congenital hearing loss, but the scope needs to be updated and redefined by removing mutation sites with a very low rate, adding new significant sites, and improvement of the technical strategies.
Connexin 26 ; Connexins/genetics* ; DNA Mutational Analysis ; Deafness/genetics* ; Genetic Testing ; Hearing Loss/genetics* ; Humans ; Infant, Newborn ; Mutation ; Neonatal Screening

Objective. The purpose of this study is to identify the incidence rate of 'refer' result in neonates born to diabetic mothers and to determine the association of maternal diabetes and the initial 'refer' result. Methods. This was a retrospective cross-sectional study which included neonates who had hearing screening test using transient-evoked otoacoustic emissions test (TEOAE) on both ears at the Philippine General Hospital Ear unit during three weeks. We obtained the demographic characteristics, presence/absence of maternal diabetes, and OAE results. Results. Among the 150 neonates, ten were born to diabetic mothers, with an age range of 2-8 days old. Forty percent of neonates of diabetic mothers had an initial 'refer' result compared with 7.9% of nondiabetic mothers' neonates. After logistic regression analysis, there is a significant association between maternal diabetes and initial 'refer' result in OAE with a p-value <0.05. If the mother is diagnosed with diabetes (gestational/pre-gestational), the odds of having an initial 'refer' result in the hearing screening is 2x higher. The odds can range from 2-43 times. Conclusion. The incidence rate of an initial 'refer' result in neonates of diabetic mothers is 40%. There is a significant association between maternal diabetes and the initial 'refer' result in the OAE test.
Infant, Newborn ; Humans ; Mothers ; Diabetes, Gestational ; Hearing Loss ; Mass Screening ; Risk Factors ; Hearing

OBJECTIVES.: Neonatal hyperbilirubinemia is considered one of the most common causative factors of hearing loss. Preterm infants are more vulnerable to neuronal damage caused by hyperbilirubinemia. This study aimed to evaluate the effect of hyperbilirubinemia on hearing threshold and auditory pathway in preterm infants by serial auditory brainstem response (ABR). In addition, we evaluate the usefulness of the unconjugated bilirubin (UCB) level compared with total serum bilirubin (TSB) on bilirubin-induced hearing loss. METHODS.: This study was conducted on 70 preterm infants with hyperbilirubinemia who failed universal newborn hearing screening by automated ABR. The diagnostic ABR was performed within 3 months after birth. Follow-up ABR was conducted in patients with abnormal results (30 cases). TSB and UCB concentration were compared according to hearing threshold by ABR. RESULTS.: The initial and maximal measured UCB concentration for the preterm infants of diagnostic ABR ≥40 dB nHL group (n=30) were statistically higher compared with ABR ≤35 dB nHL group (n=40) (P=0.031 and P=0.003, respectively). In follow-up ABR examination, 13 of the ABR ≥40 dB nHL group showed complete recovery, but 17 had no change or worsened. There was no difference in bilirubin level between the recovery group and non-recovery group. CONCLUSION.: UCB is a better predictor of bilirubin-induced hearing loss than TSB in preterm infants as evaluated by serial ABR. Serial ABR testing can be a useful, noninvasive methods to evaluate early reversible bilirubin-induced hearing loss in preterm infants.
Auditory Pathways ; Bilirubin ; Evoked Potentials, Auditory, Brain Stem ; Follow-Up Studies ; Hearing ; Hearing Loss ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal ; Infant, Newborn ; Infant, Premature ; Mass Screening ; Neurons ; Parturition

PURPOSE: To investigate clinical markers for the diagnosis of congenital cytomegalovirus (CMV) infection and determine the correlation between abnormal newborn hearing screening results and asymptomatic congenital CMV infection. METHODS: Medical records of newborns with congenital CMV infection, born at Cheil General Hospital & Women's Healthcare Center from July 2008 to June 2018, were retrospectively reviewed. Infants with congenital CMV infection were classified into “symptomatic,” “asymptomatic,” and “asymptomatic with isolated abnormal automated auditory brainstem response (AABR)” groups. Clinical data were analyzed based on this classification. RESULTS: Among the 59,424 live births, congenital CMV infection was found in 25 neonates, including 19 symptomatic (0.03%) infants, two asymptomatic, and four asymptomatic with isolated abnormal AABR. Diagnostic clues for the identification of congenital CMV infection were intrauterine growth restriction (IUGR), including microcephaly in 10 infants (40.0%), abnormal AABR in four (16.0%), initial complicated signs in four (16.0%), and abnormal findings on brain ultrasonography in three (12.0%). Other less common markers included petechiae, abnormal findings on antenatal ultrasonography, and co-twin with CMV infection. During the recent 10 years, 53,094 of 59,424 newborns (89.3%) had AABR for hearing screening and 493 (0.9%) did not pass. Among them, 477 (96.8%) were screened for CMV, and results were positive for seven (1.5%). Among the seven infants, four had asymptomatic congenital CMV infection. Overall, 0.8% of the newborns with abnormal AABR (four of 477 infants) were diagnosed as having asymptomatic congenital CMV infection. CONCLUSION: The incidence of symptomatic congenital CMV infection was 0.03%, and 0.8% of infants who failed in the newborn hearing screening tests had asymptomatic congenital CMV infection. The most common clinical marker to diagnose congenital CMV infection was IUGR, including microcephaly, and the second isolated marker was abnormal AABR.
Biomarkers ; Brain ; Classification ; Cytomegalovirus Infections ; Cytomegalovirus ; Delivery of Health Care ; Diagnosis ; Evoked Potentials, Auditory, Brain Stem ; Fetal Growth Retardation ; Hearing ; Hospitals, General ; Humans ; Incidence ; Infant ; Infant, Newborn ; Live Birth ; Mass Screening ; Medical Records ; Microcephaly ; Purpura ; Retrospective Studies ; Ultrasonography

OBJECTIVES: To review the status of newborn hearing screening (NHS) and to investigate the effect of the examiners on NHS tests to help the quality control of NHS at a general hospital in a city. METHODS: The charts of newborns from January 2015 to March 2016 and from August 2016 to October 2017 were retrospectively reviewed. We compared the results of tests performed by several examiners(group 1) with those performed by one audiologist (group 2) using the same automated auditory brainstem response test. RESULTS: The screening rate and referral rate were not significantly different between group 1 and group 2. The confirmatory test rate was higher in the group 2, but it was not significant. In group 1, the number of tests performed 3 or more times in one ear at one time was significantly higher. The number of tests performed in only one ear at one time was higher in group 2. The screening rate within one month after birth was 64.21%, referral rate was 7.32%, confirmatory test rate within 3 months after birth was 21.74%, and the prevalence of hearing loss was 1.46%. CONCLUSIONS: There was no significant difference of results depending on the examiners. In order to make proper screening test, it is necessary to periodically educate the examiner and to instruct the examiner by the supervisor doctors.
Ear ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; Hearing* ; Hospitals, General* ; Humans ; Infant, Newborn* ; Mass Screening* ; Parturition ; Prevalence ; Quality Control ; Referral and Consultation ; Retrospective Studies