Usher syndrome (USH) is an autosomal recessive disorder comprising of bilateral sensorineural hearing loss, progressive loss of vision due to retinitis pigmentosa (RP), and variable vestibular dysfunction. It is the most frequent cause of deafness and concurrent blindness in schools for the deaf-blind, 1 with a prevalence of 1/16 000 to 1/50000 in various populations. 2 The majority of Usher syndrome cases can be clinically classified into three subtypes. 3 4 USH type I (USH1; OMIM 276900, 276903, 276904, 601067, 602097, 602083 and 606943) is characterised by profound prelingual sensorineural hearing loss, vestibular areflexia, and prepubertal onset of RP. USH type II (USH2; OMIM 276901, 276905 and 605472) is characterised by moderate to severe hearing impairment, no vestibular impairment, and onset of RP in the first or second decade of life. USH type III (USH3; OMIM 276902) is characterised by progressive, post-lingual hearing loss, variable onset and severity of RP, with or without vestibular dysfunction. Atypical forms of Usher syndrome associated with mutations in USH1B and USH1D have also been reported. 5–7 There is progression of hearing loss in some of these atypical cases, making them potentially difficult to clinically distinguish from USH3.

USH3 was originally thought to be very rare, accounting for at most a few percent of the total USH population, until Pakarinen and coworkers found that up to 40% of the USH cases in Finland were consistent with USH3. 4 Difficulty in accurately detecting the progression of hearing loss may account for the lower frequency of reported USH3 cases outside of Finland. In the Finnish USH3 cohort, hearing loss was diagnosed before the age of 10 years in most patients, but up to the age of 40 years in some patients, with moderate to severe hearing threshold elevations at the time of detection. The mean hearing threshold (80 dB HL) in the USH3 cohort was lower than that in USH1 but higher than in USH2. The rate of progression varied greatly, with 42% of patients having final hearing thresholds greater than 90 dB HL (profound), and the time interval since onset of hearing loss significantly correlated with the final hearing level. 4 8 Vestibular function was abnormal in 50% of the patients. 4 8 Average age of diagnosis of RP in the Finnish cohort ranged from 3 to 51 years (mean 17 years) with both visual fields and visual acuity reaching minimal levels by 40 years of age and progression of visual acuity loss not significantly differing from the other USH types. 8 Similarly, visual findings are not useful for differentiating between USH1 and USH2. 9 It thus appears that progression of hearing loss is the key discriminatory feature between USH3 and USH1 or USH2. One USH3 locus, USH3A on chromosome 3q25, has been identified. 10USH3A expression has been detected in the cochlea and retina, although its function is unknown. 11 12 Nine mutations causing disease have so far been identified in USH3A. 10–12 Y176X (also referred to as Finmajor) is a nonsense mutation responsible for most of the USH3 cases among