Founder variant in OTOG causing non-syndromic sensorineural hearing loss in Irish traveller population.

Authors

Aoife Flynn, Rebecca Finnegan, Aisling Stafford, Ivan Keogh, Andrew Green, Sally Ann Lynch, Nicholas M Allen, Aisling Lyons, Kathleen Mary Gorman

Published in

Journal of medical genetics. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

Deafness is a common multifactorial sensory disorder with numerous underlying causes (genetic, environmental) and a broad range of impact on humans. To date, 156 non-syndromic hearing loss-associated genes have been identified (DFN) and 75%-80% follow a recessive inheritance pattern (DFNB). OTOG (MIM: 604487, chr11:17,547,259-17,646044, GrCh38) encodes otogelin, a non-collagenous protein specific to the inner ear tectorial membrane. Biallelic pathogenic variants in OTOG result in mild to moderate autosomal recessive non-syndromic SNHL (DNF18B). To date, only 41 families (63 individuals) have been reported in the literature.We report an additional seven families from the Irish Traveller population (16 individuals), with a recurrent homozygous variant in OTOG (c.3700C>T; p.Arg1234*) causing non-syndromic early-onset SNHL. The median current age is 9.5 years (IQR: 5.75-14.5 years). Two-thirds (n=11) were identified after failing newborn hearing screening, with others referred due to speech delay. All individuals have mild to moderate SNHL, with a characteristic U-shaped or 'cookie bite' audiogram. Similar to previously reported cases of OTOG-associated SNHL, in our cohort, SNHL was non-progressive even in our adult patients. There were no features of vestibular dysfunction or neurodevelopmental impairment.We reviewed all reported cases to date, in addition to our families (n=79). We demonstrate that protein-truncating variants are scattered throughout the length of the OTOG protein. However, pathogenic missense variants occur only in key domains such as vWD and trypsin inhibitor-like cysteine-rich domains.This report highlights a founder variant in OTOG within the Irish Traveller population. Clinicians should ensure that this is requested in all infants who fail newborn screening from this ethnicity.

PMID:
42642215
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

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