Hearing and Hearing Loss Progression in Patients with GJB2 Gene Mutations: A Long-Term Follow-Up

Abstract

We aimed to investigate whether the degree of hearing loss with GJB2 mutations could be predicted by distinguishing between truncating and non-truncating mutations and whether the genotype could predict the hearing loss level. Additionally, we examined the progression of hearing loss in individuals monitored for over 2 years for an average of 6.9 years. The proportion of truncating mutations was higher in patients with profound and severe hearing loss, but it was not accurate enough to predict the degree of hearing loss. Via genotype analysis, mutations of the p.Arg143Trp variants were associated with profound hearing loss, while mutations of the p.Leu79Cysfs*3 allele exhibited a wide range of hearing loss, suggesting that specific genotypes can predict the hearing loss level. Notably, there were only three cases of progression in four ears, all of which involved the p.Leu79Cysfs*3 mutation. Over the long-term follow-up, 4000 Hz was significant, and there was a trend of progression at 250 Hz, suggesting that close monitoring at these frequencies during follow-up may be crucial to confirm progression. The progression of hearing loss was observed in moderate or severe hearing loss cases at the time of the initial diagnosis, emphasizing that children with this level of hearing loss need regular follow-ups.

Keywords: GJB2; hearing loss; p.Leu79Cysfs*3; predictive; progressive.

Figure 1

Hearing changes in 4 ears in 3 cases with progressive hearing loss. Threshold progression of more than 10 dB from initial hearing evaluation to final follow-up in 4 ears. Black and black dotted lines indicate the same patients.

Figure 2

(a) Thresholds for each frequency and quadrant average according to the number of years since the start of the follow-up observation. The relationship between the hearing threshold (y-axis) and the number of years of follow-up (x-axis) was averaged only for cases that could be followed for more than one year. Hearing changes were evaluated at 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, and quadrants. N is case number. Date indicates mean ± SEM. (b) Frequency and quartile mean hearing thresholds for each case age. Date indicates mean ± SEM.

Figure 3

Threshold changes by frequency. Expressed as the number of ears that worsened by more than 10 dB, remained unchanged, or improved by more than 10 dB threshold at the point of the initial frequency-specific hearing test and at the last examination.