Abstract
Usher syndrome is an inherited and irreversible disease that manifests as retinitis pigmentosa (RP) and bilateral neurosensory hearing loss. Mutations in Usherin 2A (USH2A) are not only a frequent cause of Usher syndrome, but also nonsyndromic RP. Although gene- and cell-based therapies are on the horizon for RP and Usher syndrome, studies characterizing natural disease are lacking. In this retrospective analysis, retinal function of USH2A patients was quantified with electroretinography. Both groups had markedly reduced rod and cone responses, but nonsyndromic USH2A patients had 30 Hz-flicker electroretinogram amplitudes that were significantly higher than syndromic patients, suggesting superior residual cone function. There was a tendency for Usher syndrome patients to have a higher distribution of severe mutations, and alleles in this group had a higher odds of containing nonsense or frame-shift mutations. These data suggest that the previously reported severe visual phenotype seen in syndromic USH2A patients could relate to a greater extent of cone dysfunction. Additionally, a genetic threshold may exist where mutation burden relates to visual phenotype and the presence of hearing deficits. The auditory phenotype and allelic hierarchy observed among patients should be considered in prospective studies of disease progression and during enrollment for future clinical trials.
Highlights
Usher syndrome was thought to affect approximately 1 in 25,000 individuals, but recent epidemiologic data suggest a higher prevalence[16]
A total of 10 patients were diagnosed with Usher syndrome type IIA and 10 patients were diagnosed with recessive nonsyndromic RP (NSRP) based on clinical history, family history, dilated fundus exam, presence or absence of subjective hearing loss, and genetic confirmation of two or more Usherin 2A (USH2A) mutations
In NSRP patients, one eye was less than 20/100, which was in the context of cystoid macular edema (CME)
Summary
Usher syndrome was thought to affect approximately 1 in 25,000 individuals, but recent epidemiologic data suggest a higher prevalence[16]. This could be due in part to cases in which there is a subtle hearing phenotype, resulting in an incomplete diagnosis of isolated RP. A multi-center analysis of a large USH2A patient cohort found different visual outcomes in patients with Usher syndrome compared to NSRP24. While the rod response aids in diagnosis and is typically severely diminished or completely extinguished in Usher syndrome and RP, the 30 Hz-flicker is useful for assessing retinal function in clinical practice, as cones are affected later in the disease course[26, 27, 31, 32]. The mutation spectrum was assessed in this cohort of USH2A patients and compared to the findings of previous studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
