Genetic background in late-onset sensorineural hearing loss patients

Abstract

Genetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.

Revisiting Genetic Epidemiology with a Refined Targeted Gene Panel for Hereditary Hearing Impairment in the Taiwanese Population

“…A possible explanation for this is that we developed the 30-gene panel on the basis of our previous epidemiological studies, in which the majority of the study population was aged less than 40 years [ 13 ]. It has been reported that late-onset SNHI might be associated with more diverse genetic causes [ 41 , 42 ]. Owing to the complex genetic underpinnings, a more comprehensive NGS may be warranted to address late-onset SNHI.…”

Clinical Impact of Genetic Diagnosis of Sensorineural Hearing Loss in Adults

“…A recent 2022 study performed by Uehara et al (42) analyzed 48 Japanese patients with late-onset bilateral SNHL and identified the potential genetic causes of HL in 29 cases (60.4%), with mitochondrial mutations being the most prevalent variants (7 of 48). Differences about higher diagnostic rate and prevalent genetic variants between our cohorts might be explained because many of their cases had multiple affected family members enrolled, and above all with maternal family history of suspected mitochondrial disorders.…”

Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy

“…The most common underlying etiologies are genetic, age-related, noise-induced, and drug-related. 2,3 The widespread prevalence of SNHL, which is increasing with aging populations, highlights the need to develop safe restorative and preventative treatments. [4][5][6][7][8] Local application of drugs to the ear has gained clinical acceptance through transtympanic injection to the middle ear.…”