Genotypes and clinical phenotypes of pediatric patients with NOG variants: Middle ear surgical outcomes from a Tertiary Center in South Korea.

Objective: Although NOG variants are linked to congenital stapes fixation and conductive hearing loss (CHL), little is known about middle ear surgery outcomes and the characteristics of accompanying inner ear anomalies. We explored auditory phenotypes in patients with NOG variants, with a focus on the outcomes of middle ear surgery.

Methods: This study included 11 patients from five unrelated Korean families harboring NOG variants. Genomic investigations were conducted using whole-exome sequencing and whole-genome sequencing. The clinical phenotypes, including pre- and postoperative audiological profiles, radiological abnormalities, and other comorbidities, were analyzed.

Results: The average age at genetic testing was 8.2 years (range, 0-13 years). Two previously reported NOG variants (c.509C > T:p.Pro170Leu and c.252dup:p.Glu85ArgfsTer97) and three novel NOG variants, including the c.187G > T: p.Glu63Ter and two cryptic large deletion within the 17q22.2 region, were identified. All patients exhibited non-progressive CHL. Inner ear anomalies were documented in two patients, with variations such as cochlea and vestibular dysplasia. In this study, seven ears of four patients underwent stapedotomy, resulting in a significantly reduced air-bone gap of 10.18 ± 1.48 dB (P = 0.016), with sustained improvement. Conversely, patients carrying p.Pro170Leu variant, which is associated with poor outcomes for middle ear surgery, were excluded from surgical consideration.

Conclusion: We expanded the spectrum of genotypes and auditory phenotypes associated with NOG variants. Surgical intervention for CHL underlying NOG variants elicits favorable outcomes. However, clinicians should consider the potential for poor prognosis in certain NOG variants. Collectively, identifying NOG variants could guide the treatment strategies to improve CHL.