Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 2:12:637096.
doi: 10.3389/fgene.2021.637096. eCollection 2021.

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

Luhang Cai  1 , Ya Liu  1 , Yaping Xu  1 , Hang Yang  2 , Lihui Lv  3 , Yang Li  4 , Qiongqiong Chen  1 , Xiaojiang Lin  5 , Yihui Yang  6 , Guangwei Hu  7 , Guofeng Zheng  8 , Jing Zhou  9 , Qiyong Qian  10 , Mei-Ai Xu  11 , Jin Fang  12 , Jianjun Ding  13 , Wei Chen  1 , Jiong Gao  14
Affiliations

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

Luhang Cai et al. Front Genet. .

Abstract

Purpose: 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.

Methods: 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 CDH23, COL11A1, DFNA5, DFNB59, DSPP, GJB2, GJB3, KCNJ10, MT-RNR1, MT-TL1, MT-TS1, MYO15A, MYO7A, OTOF, PCDH15, SLC26A4, SOX10, TCOF1, TMC1, USH1G, WFS1, and WHRN using next-generation sequencing. Newborns who failed to have genetic mutations or hearing screening were diagnosed audiologically at the age of 6 months.

Results: 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 GJB2, GJB3, SLC26A4, 12SrRNA, and TMC1 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 GJB2 was increased by 97.2%, SLC26A4 by 21% and MT-RNR1 by 150%. The most common mutation variants were GJB2c.235delC and SLC26A4c.919-2A > G, followed by GJB2c.299_300delAT. Homoplasmic mutation in MT-RNR1 was the most common, including m.1555A > G, m.961T > C, m.1095T > C. All these infants have passed routine hearing screening. The positive rate of MT-RNR1 mutation was significantly higher in newborns with high-risk factors of maternal pregnancy.

Conclusion: 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 > G, and m.1555A > 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.

Keywords: deafness; genetic deafness; genetic screening; hearing screening; newborn deafness.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
A technical route of deafness genetic screening.
FIGURE 2
FIGURE 2
The hearing outcomes of newborns with positive genotypes.
FIGURE 3
FIGURE 3
Comparison of the positive rates of genetic screening in 12 regional hospitals of Zhejiang Province.
FIGURE 4
FIGURE 4
Comparison of high-risk and non-high-risk pregnancy in deafness gene mutations.
See this image and copyright information in PMC

References

    1. Barbarino J. M., McGregor T. L., Altman R. B., Klein T. E. (2016). PharmGKB summary: very important pharmacogene information for MT-RNR1. Pharmacogenet. Genomics 26 558–567. 10.1097/FPC.0000000000000247 - DOI - PMC - PubMed
    1. Butcher E., Dezateux C., Cortina-Borja M., Knowles R. L. (2019). Prevalence of permanent childhood hearing loss detected at the universal newborn hearing screen: systematic review and meta-analysis. PLoS One 14:e0219600. 10.1371/journal.pone.0219600 - DOI - PMC - PubMed
    1. Campbell C., Cucci R. A., Prasad S., Green G. E., Edeal J. B., Galer C. E., et al. (2001). Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum. Mutat. 17 403–411. 10.1002/humu.1116 - DOI - PubMed
    1. Chen S., Liang Z., Chen B., Yao F., Huang G., Zhu J., et al. (2019). The prevalence of deafness-associated mutations in neonates: a meta-analysis of clinical trials. Int. J. Pediatr. Otorhinolaryngol. 121 99–108. 10.1016/j.ijporl - DOI - PubMed
    1. Chen T., Jiang L., Liu C., Shan H., Chen J., Yang B., et al. (2014). Update of the spectrum of GJB2 mutations in 107 patients with nonsyndromic hearing loss in the Fujian population of China. Ann. Hum. Genet. 78 235–242. 10.1111/ahg.12062 - DOI - PubMed