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

Homozygous truncating founder variant OTOG c.3700C>T, p.Arg1234Ter; OTOG encodes otogelin, a non-collagenous protein specific to the inner ear tectorial membrane.

One hundred and fifty-six non-syndromic hearing loss genes have been identified to date, 75-80% of them recessive, and biallelic OTOG variants cause mild to moderate sensorineural hearing loss so far described in only 41 families (63 individuals). The authors report seven additional families from the Irish Traveller population, 16 individuals homozygous for the same OTOG c.3700C>T, p.Arg1234Ter variant causing early-onset sensorineural hearing loss. Median current age is 9.5 years (IQR 5.75-14.5); eleven of sixteen were identified after failing newborn hearing screening and the others after speech delay, and all have mild to moderate loss with a characteristic U-shaped or 'cookie bite' audiogram, non-progressive even in adults, without vestibular dysfunction or neurodevelopmental impairment. Reviewing all 79 reported cases including their own families shows that protein-truncating variants are scattered along the whole protein whereas pathogenic missense variants cluster in key domains, vWD and trypsin inhibitor-like cysteine-rich domains.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A recurrent founder variant in an identified population is the kind of result that is immediately actionable: the authors recommend testing OTOG c.3700C>T in any infant from this community who fails newborn hearing screening, and the genotype here predicts a stable phenotype, information directly useful to parents. The 'cookie bite' audiogram combined with non-progressive loss is a recognisable signal in clinic before any molecular result. The series remains retrospective and does not measure allele frequency in the wider Traveller population, which limits risk estimation for relatives.

Analysis by Dr Thibaut Benquey