Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Beijing Institute of Otolaryngology, Beijing, China.
Biosci Trends. 2024 Sep 16;18(4):303-314. doi: 10.5582/bst.2024.01178. Epub 2024 Aug 25.
Genetic screening of newborns for deafness plays an important role in elucidating the etiology of deafness, diagnosing it early, and intervening in it. Genetic screening of newborns has been conducted for 11 years in Beijing. It started with a chip to screen for 9 variants of 4 genes in 2012; the chip screened for 15 variants of those genes in 2018, and it now screens for 23 variants of those genes. In the current study, a comparative analysis of three screening protocols and follow-up for infants with pathogenic variants was performed. The rates of detection and hearing test results of infants with pathogenic variants were analyzed. Subjects were 493,821 infants born at 122 maternal and child care centers in Beijing from April 2012 to August 2023. Positivity increased from 4.599% for the chip to screen for 9 variants to 4.971% for the chip to screen for 15 variants, and further to 11.489% for the chip to screen for 23 variants. The carrier frequency of the GJB2 gene increased from 2.489% for the chip to screen for 9 variants and 2.422% for the chip to screen for 15 variants to 9.055% for the chip to screen for 23 variants. The carrier frequency of the SLC26A4 gene increased from 1.621% for the chip to screen for 9 variants to 2.015% for the chip to screen for 15 variants and then to 2.151% for the chip to screen for 23 variants. According to the chip to screen for 9 variants and the chip to screen for 15 variants, the most frequent mutant allele was c.235delC. According to the chip to screen for 23 variants, the most frequent mutant allele was c.109G>A. The chip to screen for 15 variants was used to screen 66.67% (14/21) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. The chip to screen for 23 variants was used to screen 92.98% (53/57) of newborns with biallelic variants in the GJB2 gene (52 cases were biallelic c.109G>A) and 25% (1/4) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. Among the infants with pathogenic variants (biallelic variants in GJB2 or SLC26A4), 20.66% (25/121) currently have normal hearing. In addition, 34.62% (9/26) of newborns who passed the hearing screening were diagnosed with hearing loss. Findings indicate that a growing number of newborns have benefited, and especially in the early identification of potential late-onset hearing loss, as the number of screening sites has increased. Conducting long-term audiological monitoring for biallelic variants in individuals with normal hearing is of paramount significance.
新生儿耳聋基因筛查在阐明耳聋病因、早期诊断和干预方面发挥着重要作用。北京已开展新生儿耳聋基因筛查 11 年。它始于 2012 年使用芯片筛查 4 个基因的 9 个变体；2018 年，该芯片筛查了这些基因的 15 个变体，现在它筛查了这些基因的 23 个变体。在当前的研究中，对三种筛查方案和对携带致病性变异婴儿的随访进行了比较分析。分析了携带致病性变异婴儿的检测率和听力测试结果。研究对象为 2012 年 4 月至 2023 年 8 月期间，北京 122 家母婴保健中心出生的 493821 名婴儿。阳性率从筛查 9 个变体的芯片的 4.599%上升到筛查 15 个变体的芯片的 4.971%，再上升到筛查 23 个变体的芯片的 11.489%。GJB2 基因的携带者频率从筛查 9 个变体的芯片的 2.489%和筛查 15 个变体的芯片的 2.422%上升到筛查 23 个变体的芯片的 9.055%。SLC26A4 基因的携带者频率从筛查 9 个变体的芯片的 1.621%上升到筛查 15 个变体的芯片的 2.015%，然后上升到筛查 23 个变体的芯片的 2.151%。根据筛查 9 个变体的芯片和筛查 15 个变体的芯片，最常见的突变等位基因是 c.235delC。根据筛查 23 个变体的芯片，最常见的突变等位基因是 c.109G>A。筛查 15 个变体的芯片用于筛查新增加的突变，对 SLC26A4 基因中存在双等位基因变异的 21 名新生儿中的 66.67%（14/21）进行了筛查。筛查 23 个变体的芯片用于筛查 GJB2 基因中存在双等位基因变异的 57 名新生儿中的 92.98%（52 例为双等位基因 c.109G>A）和 SLC26A4 基因中存在双等位基因变异的 4 名新生儿中的 25%（1/4）进行了新增加的突变筛查。在携带致病性变异（GJB2 或 SLC26A4 双等位基因变异）的婴儿中，20.66%（25/121）目前听力正常。此外，34.62%（9/26）通过听力筛查的新生儿被诊断为听力损失。研究结果表明，随着筛查点数量的增加，越来越多的新生儿受益，特别是在早期识别潜在的迟发性听力损失方面。对听力正常的双等位基因变异个体进行长期的听力学监测具有重要意义。
