Abstract：
Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafness-causing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.
摘要：
同时筛查已被证明为先天性耳聋的管理和耳毒性的预防提供了一种全面的方法。SLC26A4基因与迟发性听力损失相关，临床上备受关注。对于在SLC26A4基因中发现引起耳聋的突变的新生儿，北京市政府推出了一个芯片，用于对4个导致耳聋的基因的15个变异进行优化基因筛选，以筛选4个基因的9个变异，现在已经添加了SLC26A4基因的6种变体。为了确定包括4个基因的15个变体的筛选芯片的优势，分析了2019年和2020年听力和遗传筛查的趋势.受试者为76,460名新生儿，从2019年1月至2020年12月在北京24个妇幼保健中心同时接受听力和遗传筛查。使用瞬时诱发耳声发射（TEOAE）进行听力筛查，失真产物耳声发射(DPOAE)，或自动听觉脑干反应（AABR）。采集干血斑进行基因检测和4个基因的15个变异,即GJB2，SLC26A4，mtDNA12SrRNA，使用DNA微阵列平台筛选GJB3。听力筛查的初始转诊率从2019年的3.60％（1,502/41,690）下降到2020年的3.23％（1,124/34,770），听力筛查的总转诊率从2019年的0.57％（236/41,690）下降到2020年的0.54％（187/34,770），这表明新生儿听力筛查的假阳性率降低和北京市政府实施的预防听力损失政策产生了显着效果根据基因筛查的阳性率在2019年相似（4.970%，2,072/41,690）和2020（4.863%，1,691/34,770），最常见的突变等位基因是GJB2基因中的c.235delC，其次是c.919-2A>G在SLC26A4基因，以及GJB2基因中的c.299delAT。在这项队列研究中，71.43%(5/7)具有SLC26A4基因2个变异体的新生儿进行了新增加突变的筛查,28.57%(2/7)的SLC26A4基因2个变异体新生儿通过听力筛查,这表明，包括4个基因的15个变体的筛选芯片在早期发现听力损失方面是优越的，尤其是在SLC26A4基因突变导致耳聋的新生儿的早期鉴定中。这些发现具有临床意义。
