Abstract：
BACKGROUND: HL is the second most common congenital disability in China, and its high incidence brings a serious burden of medical and educational sequelae. HL genetic screening enables the identification of individuals with inherited HL and carriers in a large scale.
OBJECTIVE: This study aimed to measure the detection rates of hearing loss (HL)-associated gene mutations in the Gannan population. The molecular etiology and risk factors of hereditary HL were also analyzed.
METHODS: In total, 119,606 newborns from 18 districts of Gannan were enrolled in this multi-center study conducted between April 2019 and April 2021. Otoacoustic Emission (OAE) was used for primary hearing screening 3 days after birth in quiet conditions, and OAE combined with automated auditory brainstem response (AABR) was applied 29-42 days after birth for those who failed or missed the initial screening. Meanwhile, high-throughput sequencing of hotspot HL-associated mutations in GJB2, GJB3, MTRNR1, and SLC26A4 were performed.
RESULTS: Among the 119,606 newborns, 7796 (6.52%) failed the hearing screening. Genetic screening revealed that 5092 neonates (4.26%) carried HL-associated mutations. The detection rate of GJB2, SLC26A4, MTRNR1 and GJB3 mutations were 2.09%, 1.51%, 0.42% and 0.24%, respectively. The most prevalent variant was GJB2 c.235delC (1.74%). The second most prevalent variant was SLC26A4 c.919-2A > G (0.93%). The population who failed the hearing screening had a lower proportion (24.64%) of SLC26A4 gene variants compared to the population who passed (37.46%). Genetic screening identified 4612 (3.86%) carriers who were normal in hearing screenings. The concurrent hearing and genetic screening identified 480 (0.40%) neonates at high risk for hereditary HL.
CONCLUSIONS: The results of this study suggest that the concurrent hearing screening and high-throughput genetic screening would greatly improve the effectiveness of newborn HL programs. This integration also facilitates the management of congenital HL, and aids in the prevention of aminoglycoside antibiotics-induced HL.
OBJECTIVE: This study aimed to measure the detection rates of hearing loss (HL)-associated gene mutations in the Gannan population. The molecular etiology and risk factors of hereditary HL were also analyzed.
METHODS: In total, 119,606 newborns from 18 districts of Gannan were enrolled in this multi-center study conducted between April 2019 and April 2021. Otoacoustic Emission (OAE) was used for primary hearing screening 3 days after birth in quiet conditions, and OAE combined with automated auditory brainstem response (AABR) was applied 29-42 days after birth for those who failed or missed the initial screening. Meanwhile, high-throughput sequencing of hotspot HL-associated mutations in GJB2, GJB3, MTRNR1, and SLC26A4 were performed.
RESULTS: Among the 119,606 newborns, 7796 (6.52%) failed the hearing screening. Genetic screening revealed that 5092 neonates (4.26%) carried HL-associated mutations. The detection rate of GJB2, SLC26A4, MTRNR1 and GJB3 mutations were 2.09%, 1.51%, 0.42% and 0.24%, respectively. The most prevalent variant was GJB2 c.235delC (1.74%). The second most prevalent variant was SLC26A4 c.919-2A > G (0.93%). The population who failed the hearing screening had a lower proportion (24.64%) of SLC26A4 gene variants compared to the population who passed (37.46%). Genetic screening identified 4612 (3.86%) carriers who were normal in hearing screenings. The concurrent hearing and genetic screening identified 480 (0.40%) neonates at high risk for hereditary HL.
CONCLUSIONS: The results of this study suggest that the concurrent hearing screening and high-throughput genetic screening would greatly improve the effectiveness of newborn HL programs. This integration also facilitates the management of congenital HL, and aids in the prevention of aminoglycoside antibiotics-induced HL.
摘要：
背景：HL是中国第二常见的先天性残疾，它的高发病率带来了严重的医疗和教育后遗症负担。HL遗传筛选能够大规模鉴定具有遗传性HL和携带者的个体。
目的：本研究旨在测量赣南人群中听力损失（HL）相关基因突变的检出率。分析遗传性HL的分子病因和危险因素。
方法：总共，来自甘南州18个地区的119,606名新生儿参加了这项在2019年4月至2021年4月之间进行的多中心研究。耳声发射（OAE）用于出生后3天的安静条件下的主要听力筛查，对于初次筛查失败或错过的患者，出生后29-42天应用OAE联合自动听觉脑干反应（AABR）。同时,对GJB2,GJB3,MTRNR1和SLC26A4的热点HL相关突变进行高通量测序.
结果：在119,606名新生儿中，7796（6.52％）未通过听力筛查。基因筛查显示5092例新生儿(4.26%)携带HL相关突变。GJB2、SLC26A4、MTRNR1和GJB3基因突变检出率分别为2.09%,1.51%，0.42%和0.24%，分别。最普遍的变异是GJB2c.235delC(1.74%)。第二最普遍的变体是SLC26A4c.919-2A>G(0.93%)。与通过听力筛查的人群（37.46％）相比，未通过听力筛查的人群的SLC26A4基因变异比例（24.64％）较低。遗传筛查确定了4612名（3.86％）听力筛查正常的携带者。同时进行的听力和遗传筛查确定了480名（0.40％）具有遗传性HL高风险的新生儿。
结论：这项研究的结果表明，同时进行听力筛查和高通量遗传筛查将大大提高新生儿HL计划的有效性。这种整合也有助于先天性HL的管理，并有助于预防氨基糖苷类抗生素引起的HL。
目的：本研究旨在测量赣南人群中听力损失（HL）相关基因突变的检出率。分析遗传性HL的分子病因和危险因素。
方法：总共，来自甘南州18个地区的119,606名新生儿参加了这项在2019年4月至2021年4月之间进行的多中心研究。耳声发射（OAE）用于出生后3天的安静条件下的主要听力筛查，对于初次筛查失败或错过的患者，出生后29-42天应用OAE联合自动听觉脑干反应（AABR）。同时,对GJB2,GJB3,MTRNR1和SLC26A4的热点HL相关突变进行高通量测序.
结果：在119,606名新生儿中，7796（6.52％）未通过听力筛查。基因筛查显示5092例新生儿(4.26%)携带HL相关突变。GJB2、SLC26A4、MTRNR1和GJB3基因突变检出率分别为2.09%,1.51%，0.42%和0.24%，分别。最普遍的变异是GJB2c.235delC(1.74%)。第二最普遍的变体是SLC26A4c.919-2A>G(0.93%)。与通过听力筛查的人群（37.46％）相比，未通过听力筛查的人群的SLC26A4基因变异比例（24.64％）较低。遗传筛查确定了4612名（3.86％）听力筛查正常的携带者。同时进行的听力和遗传筛查确定了480名（0.40％）具有遗传性HL高风险的新生儿。
结论：这项研究的结果表明，同时进行听力筛查和高通量遗传筛查将大大提高新生儿HL计划的有效性。这种整合也有助于先天性HL的管理，并有助于预防氨基糖苷类抗生素引起的HL。
