A large cohort of Usher syndrome type 2 (USH2) patients with mutations in the ADGRV1 gene described key characteristics of functional and structural impairment  

Usher syndrome (USH) is a recessive disorder characterized by retinal degeneration and sensorineural hearing impairment with Usher syndrome type 2 (USH2) is the most frequent subtype, associated with pathogenic variants in three genes: USH2A, ADGRV1 and WHRN, estimated in 90%, 9% and 1% of USH2 patients, respectively.  While clinical presentations are known associated with ADGRV1 and WHRN, large patient cohorts are not yet described phenotypically.


However, researchers at the Eye Hospital, University Medical Centre Ljubljana and the Institut de l’audition, Institut Pasteur, Université de Paris, including several other international research groups, have now reported a phenotype with 18 ADGRV1 patients, showing that ADGRV1 and USH2A retinopathy “share all the major characteristics of functional and structural impairment”.  According to the researchers, their results are important for counseling ADGRV1 patients and their families.


The researchers recruited 18 ADGRV1 patients, including 9 male and 9 female participants with a median age 52 years (range 23–68 years) and there appeared to be no significant difference in disease severity between the two genders. According to the research team, the cohort identified a total of 27 different ADGRV1 variants in 16 independent patients and 2 additional siblings; there was no significant difference between the age at disease onset between ADGRV1 (median 30 years, range 5–46 years) and USH2A patients (18 years, range 0–55 years) (Mann–Whitney U test, p = 0.13); Kaplan–Meier survival analysis predicted that the mean age when 50% of the patients reached legal blindness based on visual acuity of 0.1 or less (1.0 logMAR or more) was 64 years for USH2A (95% CI 61–68 years) and 64 years for ADGRV1 (95% CI 60–68 years); there was a good interocular symmetry of the FAF patterns, the same FAF pattern was present in 94% (136/145) of USH2A and 88% (14/16) of ADGRV1 patients, and finally; OCT analysis showed that CME was present in 26% (35/135) of USH2A and 31% (5/16) of ADGRV1 patients with no statistical difference in frequency between the two groups (Fisher’s Exact Test, p = 0.4).  The paper reported that, “ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina”.