Optimized concurrent hearing and genetic screening in Beijing, China: A cross-sectional study

Abstract

Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafnesscausing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.

Newborn hearing screening program in China: a narrative review of the issues in screening and management

“…In 2012, Beijing launched a demonstration project of concurrent newborn hearing and deafness genetic screening. The project screened for nine mutations in four common deafness-related genes, such as c.235delC (p.Leu79Cysfs*3), c.299_300delAT (p.His100Argfs*14), c.176_191del16 (p.Gly59Alafs*18), and c.35delG (p.Gly12Valfs*2) in the GJB2 gene (MIM: 121011); c.919-2A > G and c.2168A > G (p.His723Arg) in the SLC26A4 gene (MIM:605646); m.1555A > G and m.1494C > T in mtDNA12SrRNA (MIM: 561000); and c.538C > T (p.Arg180*) in the GJB3 gene (MIM: 603324) ( 71 ). Currently, commonly used techniques for deafness genetic screening include microarray, PCR-fluorescent probe, fluorescent PCR, fluorescent PCR melting curve, PCR and flow-through hybridization, amplification refractory mutation system, PCR melting curve, combined probe anchoring polymerization sequencing, flight mass spectrometry sequencing, screening for known deafness-causing variants based on next-generation sequencing technology, and so on.…”

“…In 2022, a large cohort study of 3,555,336 newborns reported by Zhang et al ( 78 ) showed that GJB2 gene c.235delC was the most common variant in the Chinese newborn population, followed by SLC26A4 gene c.919-2A > G, differing from those in the Ashkenazi Jewish, European, and American populations. In 2023, the current authors’ research team ascertained the advantage of a screening chip including 15 variants of four genes and found that 71.43% of newborns with two variants of the SLC26A4 gene were screened for newly added mutations and 28.57% of newborns with two variants of the SLC26A4 gene passed the hearing screening, suggesting that a screening chip including 15 variants of four genes was superior at early detection of hearing loss, especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene ( 71 ). The genetic screening identified additional children who will possibly benefit from early intervention and informed at-risk newborns and their maternal relatives of increased susceptibility to ototoxicity ( 74 ).…”