AUTHOR=Cai Luhang , Liu Ya , Xu Yaping , Yang Hang , Lv Lihui , Li Yang , Chen Qiongqiong , Lin Xiaojiang , Yang Yihui , Hu Guangwei , Zheng Guofeng , Zhou Jing , Qian Qiyong , Xu Mei-ai , Fang Jin , Ding Jianjun , Chen Wei , Gao Jiong 

TITLE=Multi-Center in-Depth Screening of Neonatal Deafness Genes: Zhejiang, China

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.637096

DOI=10.3389/fgene.2021.637096

ISSN=1664-8021

ABSTRACT=<sec><title>Purpose</title><p>The conventional genetic screening for deafness involves 9–20 variants from four genes. This study expands screening to analyze the mutation types and frequency of hereditary deafness genes in Zhejiang, China, and explore the significance of in-depth deafness genetic screening in newborns.</p></sec><sec><title>Methods</title><p>This was a multi-centre study conducted in 5,120 newborns from 12 major hospitals in the East-West (including mountains and islands) of Zhejiang Province. Concurrent hearing and genetic screening was performed. For genetic testing, 159 variants of 22 genes were screened, including <italic>CDH23</italic>, <italic>COL11A1</italic>, <italic>DFNA5</italic>, <italic>DFNB59</italic>, <italic>DSPP</italic>, <italic>GJB2</italic>, <italic>GJB3</italic>, <italic>KCNJ10</italic>, <italic>MT-RNR1</italic>, <italic>MT-TL1</italic>, <italic>MT-TS1</italic>, <italic>MYO15A</italic>, <italic>MYO7A</italic>, <italic>OTOF</italic>, <italic>PCDH15</italic>, <italic>SLC26A4</italic>, <italic>SOX10</italic>, <italic>TCOF1</italic>, <italic>TMC1</italic>, <italic>USH1G</italic>, <italic>WFS1</italic>, and <italic>WHRN</italic> using next-generation sequencing. Newborns who failed to have genetic mutations or hearing screening were diagnosed audiologically at the age of 6 months.</p></sec><sec><title>Results</title><p>A total of 4,893 newborns (95.57%) have passed the initial hearing screening, and 7 (0.14%) have failed in repeated screening. Of these, 446 (8.71%) newborns carried at least one genetic deafness-associated variant. High-risk pathogenic variants were found in 11 newborns (0.21%) (nine homozygotes and two compound heterozygotes), and eight of these infants have passed the hearing screening. The frequency of mutations in <italic>GJB2</italic>, <italic>GJB3</italic>, <italic>SLC26A4</italic>, <italic>12SrRNA</italic>, and <italic>TMC1</italic> was 5.43%, 0.59%, 1.91%, 0.98%, and 0.02%, respectively. The positive rate of in-depth screening was significantly increased when compared with 20 variants in four genes of traditional testing, wherein <italic>GJB2</italic> was increased by 97.2%, <italic>SLC26A4</italic> by 21% and <italic>MT-RNR1</italic> by 150%. The most common mutation variants were GJB2c.235delC and SLC26A4c.919-2A &gt; G, followed by GJB2c.299_300delAT. Homoplasmic mutation in <italic>MT-RNR1</italic> was the most common, including m.1555A &gt; G, m.961T &gt; C, m.1095T &gt; C. All these infants have passed routine hearing screening. The positive rate of <italic>MT-RNR1</italic> mutation was significantly higher in newborns with high-risk factors of maternal pregnancy.</p></sec><sec><title>Conclusion</title><p>The positive rate of deafness gene mutations in the Zhejiang region is higher than that of the database, mainly in GJB2c.235delC, SLC26A4 c.919-2A &gt; G, and m.1555A &gt; G variants. The expanded genetic screening in the detection rate of diseasecausing variants was significantly improved. It is helpful in identifying high-risk children for follow-up intervention.</p></sec>