To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.
Figure1 Flow chart of subjects included in the study. Patients with biallelic pathogenic mutations were defined as solved, and patients with only 1 known pathogenic mutation were considered unsolved. RP= retinitis pigmentosa. Figure2 Graphs showing cumulative incidence (%) of low vision based on (A) visual acuity of less than 0.3 and (B) GVF of less than 20 as a function of age stratified for Usher syndrome type IIa and nonsyndromic retinitis pigmentosa (RP). The cumulative incidence of low vision at 0, 20, 40, 60, and 80 years of age is indicated in the grey box below the graph. Red= Usher syndrome type IIa; black= nonsyndromic RP. Figure3 Graphs showing cumulative incidence (%) of legal blindness based on (A) visual acuity of less than 0.05 and (B) GVF of less than 10 as a function of age stratified for Usher syndrome type IIa and nonsyndromic retinitis pigmentosa (RP). The cumulative incidence of legal blindness at 0, 20, 40, 60, and 80 years of age is indicated in the grey box below the graph. Red line= Usher syndrome type IIa; black= nonsyndromic RP. Figure4 Graphs showing the relationship between mean log retinal area and age. Solid line= mixed model estimation; dashed line= confidence interval. RP= retinitis pigmentosa. Figure5 Schematic representation of the usherin protein and localization of mutations. Mutations in the first column were found only in participants with Usher syndrome type IIa. Mutations in the last column were found only in nonsyndromic retinitis pigmentosa (RP) participants. Mutations in the middle column were present in both phenotype groups. Purpose USH2A mutations are an important cause of retinitis pigmentosa (RP) with or without congenital sensorineural hearing impairment. We studied genotypephenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP. Design Clinic-based, longitudinal, multicenter study. Participants Consecutive patients with Usher syndrome type IIa (n= 152) and nonsyndromic RP (n= 73) resulting from USH2A mutations from ophthalmogenetic clinics in the Netherlands and Belgium. Methods Data on clinical characteristics, visual acuity, visual field measurements, retinal imaging, and electrophysiologic features were extracted from medical charts over a mean follow-up of 9 years. Cumulative lifetime risks of low vision and blindness were estimated using Kaplan-Meier survival analysis. Main Outcome Measures Low vision and blindness. Results Participant groups had similar distributions of gender (48% vs. 45% males in Usher syndrome type IIa vs. nonsydromic RP; P= 0.8), ethnicity (97% vs. 99% European; P= 0.3), and median follow-up time (6.5years vs. 3 years; P=0.3). Usher syndrome type IIa patients demonstrated symptoms at a younger age (median age, 15 years vs. 25 years; P < 0.001), were diagnosed earlier (median age, 26 years vs. 36.5 years; P < 0.001), and became visually impaired 13 years earlier (median age, 41 years vs. 54 years; P < 0.001) based on VF and 18 years earlier based on VA (median age, 54 years vs. 72 years; P < 0.001) than nonsyndromic RP patients. The presence of 2 truncating mutations in USH2A was associated mostly with the syndromic phenotype, whereas other combinations were present in both groups. We found novel variants in Usher syndrome type IIa (25%) and nonsyndromic RP (19%): 29 missense mutations, 10 indels, 14 nonsense mutations, 9 frameshift mutations, and 5 splice-site mutations. Conclusions Most patients with USH2A-associated RP have severe visual impairment by age 50. However, those with Usher syndrome type IIa have an earlier decline of visual function and a higher cumulative risk of visualimpairment than those without nonsyndromic RP. Complete loss of function of the USH2A protein predisposes toUsher syndrome type IIa, but remnant protein function can lead to RP with or without hearing loss. To access this article, please choose from the options below Purchase access to this article Claim Access If you are a current subscriber with Society Membership or an Account Number, claim your access now. Subscribe to this title Purchase a subscription to gain access to this and all other articles in this journal. Institutional Access Visit ScienceDirect to see if you have access via your institution. http://www.aaojournal.org/article/S0161-6420(16)00066-X/abstract?rss=yes
0 Comments
|
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
March 2017
Categories |