Cohort study reveals a recurrent homozygous OTOG founder variant causing stable sensorineural hearing loss in Irish Travellers, highlighting the utility of targeted screening.
Key Points
Investigate the clinical and molecular characteristics of a recurrent OTOG variant causing autosomal recessive non-syndromic sensorineural hearing loss in Irish Traveller families.
Assessed 16 individuals across seven Irish Traveller families presenting with non-syndromic sensorineural hearing loss (median age 9.5 years, IQR: 5.75–14.5).
Conducted a comprehensive review of all 79 globally reported cases of OTOG-related hearing loss to map variant distributions across protein domains.
All 16 individuals were homozygous for the OTOG c.3700C>T (p.Arg1234*) variant, exhibiting mild to moderate, non-progressive hearing loss with characteristic U-shaped 'cookie bite' audiograms and no vestibular dysfunction.
Analysis across 79 total cases demonstrated that protein-truncating variants disperse across the entire OTOG protein, whereas pathogenic missense variants localize strictly within vWD and trypsin inhibitor-like cysteine-rich domains.