Retinal Disease in Usher Syndrome III Caused by Mutations in the Clarin-1 Gene

Abstract

To determine the retinal phenotype of Usher syndrome type III (USH3A) caused by clarin-1 (CLRN1) gene mutations in a non-Finnish population. Patients with USH3A (n = 13; age range, 24-69) representing 11 different families were studied and the results compared with those from patients with USH2A (n = 24; age range, 17-66). The patients were evaluated by ocular examination, kinetic and static perimetry, near-infrared autofluorescence, and optical coherence tomography (OCT). Ten of 11 families had Ashkenazi Jewish origins and the N48K CLRN1 mutation. Rod function was lost in the peripheral field in the first two decades of life, but central rod function could be retained for another decade. Peripheral cone function was detectable into the third decade of life. Central cone function had a slower decline that extended for decades. Photoreceptor layer loss and features of retinal remodeling were present in retinal regions with severe visual dysfunction, even at the youngest ages tested. Central retinal structure could be normal in younger patients but structural integrity was lost in older patients. RPE disease generally paralleled photoreceptor degeneration. Comparisons between USH3A and USH2A suggested a common rod and cone phenotype but a more accelerated time course of rod loss in USH3A. USH3A and USH2A share patterns of rod and cone dysfunction and retinal structural abnormalities. Peripheral function measurements showed USH3A to be more rapidly progressive than USH2A.