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Abstract：
BACKGROUND: To analyze the genotype distribution and frequency of hearing loss genes in newborn population and evaluate the clinical value of genetic screening policy in China.
METHODS: Genetic screening for hearing loss was offered to 84,029 neonates between March 2019 and December 2021, of whom 77,647 newborns accepted the screening program with one-year follow-up. The genotyping of 15 hot spot variants in GJB2, GJB3, SLC26A4, and MT-RNR1 was performed on microarray platform.
RESULTS: A total of 3.05% (2369/77,647) newborns carried at least one genetic hearing loss-associated variant, indicated for early preventive management. The carrier frequency of GJB2 gene was the highest, at 1.48% (1147/77,647), followed by SLC26A4 gene at 1.07% (831/77,647), and GJB3 gene at 0.23% (181/77,647). GJB2 c.235delC variant and SLC26A4 IVS7-2A>G variant were the most common allelic variants with allele frequency of 0.6304% (979/155,294) and 0.3992% (620/155,294), respectively. 10 children are identified as homozygous or compound heterozygous for pathogenic variants (4 in GJB2, 6 in SLC26A4), and 7 of these infants had passed the hearing screening. Following up of the genetically screened newborns revealed that genetic screening detected more hearing-impaired infants than hearing screening alone. Genetic screening helped identify the infants who had passed the initial hearing screening, and reduced time for diagnosis and intervention of hearing aid. In addition, we identified 234 newborns (0.30%, 234/77,647) susceptible to preventable aminoglycoside antibiotic ototoxicity undetectable by hearing screening.
CONCLUSIONS: We performed the largest-scale neonatal carrier screening for hearing loss genes in Southeast China. Our results indicated that genetic screening is an important complementation to conventional hearing screening. Our practice and experience may facilitate the application and development of neonatal genetic screening policy in mainland China.
METHODS: Genetic screening for hearing loss was offered to 84,029 neonates between March 2019 and December 2021, of whom 77,647 newborns accepted the screening program with one-year follow-up. The genotyping of 15 hot spot variants in GJB2, GJB3, SLC26A4, and MT-RNR1 was performed on microarray platform.
RESULTS: A total of 3.05% (2369/77,647) newborns carried at least one genetic hearing loss-associated variant, indicated for early preventive management. The carrier frequency of GJB2 gene was the highest, at 1.48% (1147/77,647), followed by SLC26A4 gene at 1.07% (831/77,647), and GJB3 gene at 0.23% (181/77,647). GJB2 c.235delC variant and SLC26A4 IVS7-2A>G variant were the most common allelic variants with allele frequency of 0.6304% (979/155,294) and 0.3992% (620/155,294), respectively. 10 children are identified as homozygous or compound heterozygous for pathogenic variants (4 in GJB2, 6 in SLC26A4), and 7 of these infants had passed the hearing screening. Following up of the genetically screened newborns revealed that genetic screening detected more hearing-impaired infants than hearing screening alone. Genetic screening helped identify the infants who had passed the initial hearing screening, and reduced time for diagnosis and intervention of hearing aid. In addition, we identified 234 newborns (0.30%, 234/77,647) susceptible to preventable aminoglycoside antibiotic ototoxicity undetectable by hearing screening.
CONCLUSIONS: We performed the largest-scale neonatal carrier screening for hearing loss genes in Southeast China. Our results indicated that genetic screening is an important complementation to conventional hearing screening. Our practice and experience may facilitate the application and development of neonatal genetic screening policy in mainland China.
摘要：
背景：分析新生儿听力损失基因的基因型分布和频率，并评估中国基因筛查政策的临床价值。
方法：在2019年3月至2021年12月期间，对84,029名新生儿进行了听力损失遗传筛查，其中77,647名新生儿接受了筛查计划，并进行了一年的随访。在微阵列平台上对GJB2、GJB3、SLC26A4和MT-RNR1中的15个热点变体进行基因分型。
结果：总共3.05％（2369/77,647）的新生儿携带至少一种遗传性听力损失相关变异，用于早期预防管理。GJB2基因的携带频率最高，1.48%（1147/77,647），其次是SLC26A4基因，占1.07%(831/77,647)，和GJB3基因在0.23%（181/77,647）。GJB2c.235delC变体和SLC26A4IVS7-2A>G变体是最常见的等位基因变体，等位基因频率为0.6304%(979/155,294)和0.3992%(620/155,294)。分别。10名儿童被鉴定为致病性变异的纯合或复合杂合（GJB2中有4名，SLC26A4中有6名），其中7名婴儿通过了听力筛查。对经过基因筛查的新生儿进行随访后发现，与单独进行听力筛查相比，遗传筛查检测到的听力受损婴儿更多。基因筛查有助于识别通过初步听力筛查的婴儿，减少助听器的诊断和干预时间。此外,我们确定了234名新生儿(0.30%，234/77,647）易受可预防的氨基糖苷类抗生素耳毒性的影响，听力筛查无法检测到。
结论：我们在中国东南部进行了最大规模的新生儿听力损失基因携带者筛查。我们的结果表明，遗传筛查是传统听力筛查的重要补充。我们的实践和经验可以促进中国大陆新生儿遗传筛查政策的应用和发展。
方法：在2019年3月至2021年12月期间，对84,029名新生儿进行了听力损失遗传筛查，其中77,647名新生儿接受了筛查计划，并进行了一年的随访。在微阵列平台上对GJB2、GJB3、SLC26A4和MT-RNR1中的15个热点变体进行基因分型。
结果：总共3.05％（2369/77,647）的新生儿携带至少一种遗传性听力损失相关变异，用于早期预防管理。GJB2基因的携带频率最高，1.48%（1147/77,647），其次是SLC26A4基因，占1.07%(831/77,647)，和GJB3基因在0.23%（181/77,647）。GJB2c.235delC变体和SLC26A4IVS7-2A>G变体是最常见的等位基因变体，等位基因频率为0.6304%(979/155,294)和0.3992%(620/155,294)。分别。10名儿童被鉴定为致病性变异的纯合或复合杂合（GJB2中有4名，SLC26A4中有6名），其中7名婴儿通过了听力筛查。对经过基因筛查的新生儿进行随访后发现，与单独进行听力筛查相比，遗传筛查检测到的听力受损婴儿更多。基因筛查有助于识别通过初步听力筛查的婴儿，减少助听器的诊断和干预时间。此外,我们确定了234名新生儿(0.30%，234/77,647）易受可预防的氨基糖苷类抗生素耳毒性的影响，听力筛查无法检测到。
结论：我们在中国东南部进行了最大规模的新生儿听力损失基因携带者筛查。我们的结果表明，遗传筛查是传统听力筛查的重要补充。我们的实践和经验可以促进中国大陆新生儿遗传筛查政策的应用和发展。
