A prospective study of genetic screening of 2 060 neonates by high-throughput sequencing / 中华医学遗传学杂志

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.

Comparative analysis of 226 Hz and 1 000 Hz probe tone tympanometry in infants / 临床耳鼻咽喉头颈外科杂志

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.

Auditory Brainstem Responses of 1~6 Month Normal Infants / 听力学及言语疾病杂志

Objective To investigate the characteristics of click -auditory brainstem response (ABR) in nor-mal infants of 1 to 6 months old ,and to establish the normative values for latencies of Wave I ,III ,V and interpeak latencies of I- Ⅲ ,III-V and I-V for younger infants .Methods Click auditory brainstem responses were recorded from infants within 6 months :166 infants of 1 -months old(269 ears) ,141 2 -month old (226 ears) ,111 3 -months old(177 ears) ,58 4-months old(96 ears) ,78 5-months old(121 ears) and 45 6-months old(76 ears) .We compared the latencies of wave I ,III ,V and interpeak latencies of I - Ⅲ ,III-V ,I-V obtained from infants of differ-ent ages at different stimulus intensities .Results The average threshold of 1 to 6 months infants was 16 .18 ± 5 .35 dB nHL ,the average latency of Wave V was 9 .03 ± 0 .49 ms .The differences among the thresholds were statistical-ly insignificant(P>0 .05) .Wave I ,III and V were noticeable in all ears tested at 80 dB nHL .Wave I disappeared first as the stimulus intensity decreased ,and the latencies of Wave I ,III and V prolonged;on the contrary ,interpeak latencies of I -III ,III-V ,I-V shortened significantly .At the same stimulus intensity ,the latencies of Wave III , V and the interpeak latencies of I - Ⅲ ,III-V ,I-V shortened significantly except for Wave I .When comparing the differences among the testing parameters as a function of each month ,we found that there were statistically signifi-cant differences for the latencies of wave III ,V and the interpeak latencies of I -III ,III-V ,I-V before the 4 months old(P0 .05) .Conclusion It is recommen-ded that 16 .18 ± 5 .35 dB nHL be used as the normative references for the evoked threshold of click auditory brain-stem responses for 1~6 month old infants .The development of central nervous system below the inferior calicles is fast before the 4 months old .

The Effects of Different Probe Tone and Tympanometric Admittance Measurement Methods to Otitis Media Prediction / 听力学及言语疾病杂志

Objective To explore the effects of different probe tone and tympanometric admittance measure-ment methods on the diagnose of otitis media prediction ,and to provide a clinical reference for the selection of probe tones and measurement method to apply to newborn infants .Methods Tympanograms with 226 Hz and 1 000 Hz probe tones were obtained from normal infants (142 ears) and infants with otitis media (90 ears) .Mean values , standard deviations ,the 90% range and 95% mean confidence interval were recorded as the variable to observe po-tential impacts on tympanometric admittance with 226 Hz probe tone and tympanometric peak admittance with 1 000 Hz probe tone by three different measurement methods respectively according to Linder/Jerger classification ,the Baldwin classification and baseline classification adapted from Baldwin .The four indexes were tested with compara-tive analysis .The area under ROC curve simultaneous detects the normal group and otitis media group ,with refer-ences to the accuracy of the detection method to disease (including specificity and sensitivity ) .Results In 1-to -3 month group ,tympanometric admittance with 226 Hz probe tone and tympanometric peak admittance with 1 000 Hz probe tone by three different measurement methods were 0 .83 ± 0 .29 ,0 .60 ± 0 .55 ,0 .74 ± 0 .56 ,0 .90 ± 0 .59 in nom-al infants and 0 .82 ± 0 .35 ,0 .01 ± 0 .06 ,-0 .24 ± 0 .15 ,-0 .29 ± 0 .21 in infants with OME ,respectively .The areas under ROC curve of the four kinds of measurement methods were 0 .507 ,0 .896 ,0 .976 ,0 .988 ,respectively .In 4 to 6 month group ,tympanometric admittance with 226 Hz probe tone and tympanometric peak admittance with 1 000 Hz probe tone by three different measurement methods were 0 .60 ± 0 .35 ,0 .55 ± 0 .58 ,0 .76 ± 1 .0 ,0 .86 ± 0 .72 in nomal infants and 0 .36 ± 0 .24 ,0 ± 0 ,-0 .34 ± 0 .16 ,-0 .44 ± 0 .28 in infants with OME ,respectively .The areas under ROC curve of the four kinds of measurement methods were 0 .749 ,0 .888 ,0 .969 ,0 .988 in 4 to 6 month infants ,re-spectively .Tympanometric peak admittance with 1 000 Hz probe tone by three different measurement methods were significantly better than that with 226 Hz probe tone .The areas under ROC curve of tympanometric peak admittance with 1 000 Hz probe tone by baseline classification adapted from Baldwin were bigger than others and the differences were significant(P0 .05) .Conclusion Tympanometric peak admittance with 1 000 Hz probe tone were better than that with 226 Hz probe tone to assess otitis media in 1~6 month infants .The baseline classification adapted from Baldwin was appropriate for the measurement of tympanometric peak admittance with 1 000 Hz probe tone .

Effects of tympanic membrane perforation on real-ear to coupler difference / 临床耳鼻咽喉头颈外科杂志

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.