Newborn screening for deafness genes with cord blood-based multicolour melting curve analysis

Am J Otolaryngol. 2024 Dec 9;46(1):104530. doi: 10.1016/j.amjoto.2024.104530. Online ahead of print.

Abstract

Background: The purpose of the research was to examine the prevalence rates of screening for genetics and hearing simultaneously in neonates and provide scientific evidence for the beneficial application of newborn screening in the Southeast China population.

Methods: Between June 2015 and March 2023, 27,843 newborns were enrolled in the study. All participants were screened by otoacoustic emissions at 2 days of age. Fifteen variant hotspots in the four deafness genes (GJB2, GJB3, SLC26A4 and MTRNR1) were detected using multicolour melting curve analysis. Newborn screening data were also analysed.

Results: In otoacoustic emissions testing, 244 newborns (0.88 %) failed the secondary screening. According to genetic testing, 1307 (4.69 %) newborns had at least one variant. GJB2 c.235delC (2.34 %) and SLC26A4 c.919-2 A > G (0.91 %) were the major deafness-related variants in the Wenzhou area of Southeast China. In addition, a difference in the number of newborns with variants was observed between the passed and failed groups. The difference in the positive rate between the two groups was statistically significant (χ2 = 274.969, P < 0.05).

Conclusions: Newborn screening for deafness genes by cord blood-based melting curve analysis can be applied to genetic counselling, prenatal diagnosis, and genetic screening of newborns with sensorineural hearing impairment with an unknown cause. The new PCR melting curve analysis approach is more effective and more convenient than SNaPshot and MS-based assay testing. Furthermore, it has a lower cost and is more suitable for clinical testing.

Keywords: Cord blood; Gene variants; Melting curve analysis; Newborns; Nonsyndromic hearing loss; Screening.