RESUMEN
The study aims to explore the epigenetic mechanisms of neurodevelopmental impairment accompanied in chorioamniotic preterm infants. Our study included 16 full-term infants and 69 preterm infants. The methylation status of the pleomorphic adenoma gene-like 1 (PLAGL1) gene in the cord blood was determined by pyrosequencing. Brain B-ultrasonography and magnetic resonance imaging (MRI) were performed to diagnose brain injury. The activity of candidate fragments of PLAGL1 and the effect of methylation on PLAGL1 activity were evaluated by double luciferase reporter assay. The data showed that there were no differences in the methylation levels of each Cytosine-phosphate-Guanine (CpG) site of PLAGL1 between full-term and preterm infants. Within preterm infants, the methylation levels of the CpG2, CpG3, CpG4, and CpG5 sites were increased in the chorioamnionitis group compared with the no chorioamnionitis group. The areas under curves (AUCs) of the receiver operating characteristic (ROC) curves of CpG2, CpG3, CpG4, and CpG5 were 0.656, 0.653, 0.670, and 0.712, respectively. Meanwhile, the methylation level of the CpG2 site was increased in preterm babies with brain injury compared with those without brain injury, and the AUC of CpG2 was 0.648, with a sensitivity of 75.9% and a specificity of 50.0%. A double luciferase reporter assay revealed that PLAGL1 fragments had enhancer-like activity and that the methylated form of PLAGL1 weakened this activity. Thus, PLAGL1 hypermethylation in chorioamniotic preterm infants is positively correlated with brain injury. Our results suggest a potential use for PLAGL1 methylation as a biomarker in the diagnosis of brain injury.
RESUMEN
BACKGROUND: Kabuki syndrome 1 (KS1; OMIM:147920), which is characterized by distinctive dysmorphic facial features (such as arched eyebrows, long palpebral fissures with eversion of the lower lid, and large protuberant ears), intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities, is brought on by pathogenic variants in KMT2D (OMIM:602113). In this work, three individuals with novel pathogenic KMT2D gene variants had their longitudinal audiological manifestations and ear structural characteristics outlined. METHODS: The longitudinal audiological data from neonatal hearing screening and a battery of several hearing tests were evaluated. The battery of hearing tests included tympanometry, distortion product otoacoustic emission (DPOAE), click-evoked air-conduction auditory brain-stem response (AC-ABR), click-evoked bone-conduction auditory brain-stem response (BC-ABR), narrow band CE-chirp auditory steady-state response (NB CE-chirp ASSR), and pure-tone audiometry (PTA). Phenotype identification and whole exome sequencing (WES) were performed on recruited individuals. RESULTS: All three patients (two females and on male; last evaluations at 14 months, 11 months, and 5.7 years, respectively) failed the newborn hearing screening, and the audiological follow-up data revealed mild to profound fluctuating hearing loss, which was directly influenced by the incidence and severity of otitis media with effusion (OME). When OME occurred, the AC-ABR thresholds increased from 30-75 dBnHL to 45-90 dBnHL. The threshold for the BC-ABR and BC-PTA was between 25 and 50 dBnHL, indicating mild to moderate sensorineural hearing loss (SNHL). The high-resolution computed tomography (HRCT) pictures indicated that all three patients had middle and inner ear abnormalities. Middle ear anomalies showed as diminished mastoid gasification and ossicle dysplasia. Cochlear dysplasia, a dilated vestibule, fusion of the vestibule with the horizontal semicircular canals, and a short and thick horizontal semicircular canal were visible on images of the inner ear. This study recruited three individuals with three novel pathogenic variants (c.5104C>T, c.10205delA, and c.12840delC) of KMT2D who were identified at ages 27 days, 2 months, and 5.5 years. CONCLUSIONS: Hearing characteristics of three individuals with three novel pathogenic variants of KMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.
Asunto(s)
Anomalías Múltiples , Cara/anomalías , Pérdida Auditiva , Enfermedades Hematológicas , Enfermedades Vestibulares , Recién Nacido , Femenino , Humanos , Masculino , Audición/fisiología , Pruebas Auditivas/métodos , Anomalías Múltiples/genética , Pérdida Auditiva/genéticaRESUMEN
BACKGROUND: Electrophysiological tests are often used to evaluate hearing loss in infants and young children with conductive hearing loss, no matter to quantify or characterize. However, there are advantages and disadvantages associated with the various electrophysiological tests that are currently available. Therefore, there is no gold standard test. This study aimed to compare the value of narrow-band (NB) CE-Chirp-induced auditory steady-state response (ASSR) and auditory brainstem response (ABR) for assessing hearing thresholds in children with conductive hearing loss. We hope to identify an effective electrophysiological testing method to evaluate conductive hearing loss and provide a reference for clinical hearing assessment of infants with conductive hearing loss. SUBJECTS: and Methods: We selected 27 children (41 ears) aged 3-6 years with otitis media with effusion (OME). Within 1 day, they underwent behavioral audiometry and NB CE-Chirp-induced ASSR and ABR tests in sequence. Pearson's correlation analysis was performed to compare behavioral audiometry thresholds and ASSR and ABR response thresholds at 500, 1000, 2000, and 4000 Hz. RESULTS: The behavioral audiometry thresholds of all children were strongly correlated with the response thresholds of the two electrophysiological tests, with correlation coefficients of 0.659, 0.605, 0.723, and 0.857 for ASSR, and 0.587, 0.684, 0.753, and 0.802 for ABR. The proportion of children with a difference of ≤10 dB between ASSR and behavioral audiometry thresholds or between ABR and behavioral audiometry thresholds was not high, especially in the low frequencies. ABR results were superior to ASSR results in terms of predicting actual hearing levels. At 0.5, 1, 2, and 4 kHz, the average differences between the behavioral hearing thresholds and ASSR thresholds in the 41 ears were 5.6, 5.7, 2, and 5.6 dB, respectively. The average differences between behavioral hearing thresholds and ABR thresholds was -5.6, -1.4, -6.8, and 3.2 dB, respectively. The hearing loss configuration of the ASSR exhibited a peaked pattern, similar to behavioral audiometry, whereas the ABR exhibited an ascending pattern. The time to perform the single-ear ASSR test was 5.9 min, whereas the ABR test took 17.0 min. CONCLUSION: ASSR and ABR induced by the NB CE-Chirp correlated well with behavioral audiometry in children with conductive hearing loss. The NB CE-Chirp ASSR has advantages in terms of testing time and hearing configuration evaluation, whereas ABR has better reliability than ASSR. However, the stability of ASSR and ABR induced by the NB CE-Chirp is poor, and the thresholds obtained cannot replace behavioral audiometry in evaluating the true hearing of children with conductive hearing loss. However, ASSR and ABR can be used as auxiliary tests for cross-validation.
Asunto(s)
Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva , Lactante , Niño , Humanos , Preescolar , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva Conductiva/diagnóstico , Pérdida Auditiva Conductiva/etiología , Reproducibilidad de los Resultados , Estimulación Acústica/métodos , Umbral Auditivo/fisiología , AudiciónRESUMEN
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.
Asunto(s)
Sordera , Deficiencia de Glucosafosfato Deshidrogenasa , Pérdida Auditiva Sensorineural , Niño , Recién Nacido , Humanos , Femenino , Estudios Prospectivos , Conexinas/genética , Conexina 26/genética , Mutación , Transportadores de Sulfato/genética , Análisis Mutacional de ADN , Pruebas Genéticas/métodos , Sordera/genética , Tamizaje Neonatal/métodos , Pérdida Auditiva Sensorineural/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Miembro 5 de la Familia 22 de Transportadores de Solutos/genéticaRESUMEN
OBJECTIVE: To analyze the judgement standard and evaluate the diagnostic value of the low frequency and high frequency tympanometry in infants with otitis media. METHOD: Tympanograms for admittance with 226 Hz and 1 000 Hz probe tones and resonant frequency were obtained from normal infants (195 cases, 321 ears) and infants with otitis media(122 cases, 171 ears). The mean, standard deviation, median, 5% quantile, 95% quantile and 95% confidence interval of peak admittance, gradient and resonant frequency were measured and calculated in different age groups. The significant differences of 1000 Hz peak admittance, 226 Hz peak admittance and gradient between normal infants and infants with otitis median were analyzed using SPSS 11.0. The false positive rate and the false negative rate of different age groups in infants with otitis media were evaluated according to such judgement standards as 1000 Hz peak admittance, 226Hz peak admittance or gradient. RESULT: The false positive rate and the false negative rate of the 1000 Hz probe tone tympanometry in infants with otitis media unter one year of age were 3.07% and 1.84% as the normal range of positive peak was more than 0.2 mmho. The false positive rate and the false negative rate of the 1000 Hz probe tone tympanometry in infants with otitis media aged 1-2 years and aged 2-3 years were 3.26%, 5.26% and 1.52%, 0.00% respectively,as the normal range of positive peak was more than 0.3 mmho. These was no significant difference in the gradient with 226 Hz probe tone between normal infants and infants with otitis median under one year of age. The false positive rate and the false negative rate of the 226 Hz probe tone tympanometry in infants with otitis media aged 1-2 years and aged 2-3 years were 44.57%, 31.58% and 16.67%, 6.67% respectively, as the gradient with 226 Hz probe tone was a judgement standard. CONCLUSION: (1) The diagnostic accuracy of tympanometry with 1000 Hz probe tone for otitis media in infants younger than 3 years of age exceeded 226 Hz probe tone tympanometry, the 1000 Hz probe tone tympanometry is suggested to the evaluation of middle ear function in infants before 3 years. (2) It is reasonable that the normal range of positive peak is more than 0.2 mmho in infants unter one year of age and the normal range of positive peak is more than 0.3 mmho in infants aged 1-3 years.
Asunto(s)
Pruebas de Impedancia Acústica/métodos , Pruebas de Impedancia Acústica/estadística & datos numéricos , Estudios de Casos y Controles , Humanos , Lactante , Recién Nacido , Otitis Media/diagnóstico , Valores de ReferenciaRESUMEN
OBJECTIVE: To investigate the effects of tympanic membrane perforation on real-ear to coupler difference (RECD) in adults. METHOD: RECD was measured in 34 ears with dry tympanic membrane perforation, 34 normal subjects served as controls. RESULT: There was significant difference (P<0.05) below 1 kHz (including 1 kHz) and in 4 kHz between experimental group and control group. For perforated ears, RECD was 3.5-15 dB less from 250 Hz to 1 kHz while the values of RECD was negative from 250 Hz to 750 Hz. A larger standard deviation was found in experimental group. The mean intra-subject standard deviation was 4.4 dB in experimental group as contrasted with 1.4 dB in control group. The equivalent ear canal volume appeared to be negatively correlated with the RECD reduction below 0.75 kHz and no correlation above 1 kHz. The more the equivalent ear canal volume, the smaller the RECD. It was found that the size of tympanic membrane perforation had no effect on RECD. CONCLUSION: It is recommended to perform real-ear measurement individually instead of using the age-appropriate average values, and to increase low frequency gain appropriately when fitting hearing aids for patients with dry tympanic membrane perforation.
Asunto(s)
Audífonos , Perforación de la Membrana Timpánica/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Pruebas Auditivas , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To investigate the hearing change and the characteristic of hearing thresholds of the infants failing in the hearing screening. METHOD: ABR,DPOAE and acoustic immittance were used to test infants failing in the screening in their third month and the sixth month, whose results were compared. RESULT: In the third month the false positive rate of DPOAE test was 9.6%. Comparing with the results tested in the third month, the degree of severe hearing loss retested in the sixth month did not change much. But the percentage of the slight-moderate hearing loss improvement to normal or better was higher. Comparing ABR threshold result in the third month and that in the sixth month, t = 3.496, P <0.01 in the left ear, and t = 5.572, P <0.01 in the right ear, respectively. There was significant difference between these results. CONCLUSION: The new-borns failing DPOAE can not be just considered to identifying hearing loss,and it must be with the ABR to make the diagnosis. It is feasible to diagnose severe-profound hearing loss in the third month and interfere before the sixth month, but the infants with mild-moderate hearing loss must undertake the auditory tests more than twice and be followed up in more than half a year, then we can make diagnosis according to the audiologic evaluations results and the daily behaviors.