A: Improvement of diagnostic

Component A: Improvement of diagnostic

Tasks of Component A are improvement of Usher clinical diagnosis, both using standard examination methods and novel techniques, elaboration of significant markers for Usher disease progression that would be utilized for future therapy trials and development of EUR-USH database for phenotypically and genotypically well characterized Usher patients’ cohorts in Europe.

We initiated a multinational clinical study to enhance methods of clinical and genetic diagnosis in Usher patients across Europe (P2, P4). This clinical protocol will be disseminated by AIBILI, as Coordinating Centre of EVICR.net – European Vision Institute Clinical Research Network, through its 79 Clinical Sites of Excellence in Ophthalmology. Eur-USH study is currently recruiting participants (http://clinicaltrials.gov/, NCT01954953).

For each patient we have tailored a set of precise USH standard operating procedures: visual acuity, kinetic and static perimetry, fundus color photography, electrophysiology recordings. Special emphasis placed on imaging techniques: autofluorescence, optical coherence tomography and adaptive optics. Furthermore, we will optimize novel functional techniques using psychophysics (pupilometry and color vision tests). The collaborative efforts between partners will result in an innovative USH screening battery for early diagnosis assessment and most significant markers for disease progression elaboration (P3, P4). Multimodal mapping modes suitable for observation of retinal structure/function related changes will be developed (P4). Genotype and phenotype correlations will be performed (P3, P4, P5). Data will provide insights into time window for upcoming therapies.

Furthermore, EUR-USH is offering molecular diagnosis for Usher syndrome. Comprehensive analysis of the Usher genes have been developed over these years to offer the most efficient molecular studies with a mutant detection rate >90% (P5). This has been shown to be possible, despite the high genetic heterogeneity, by the development of tools allowing the detection and interpretation of all types of mutations (point mutations, large genomic rearrangements, mutations located deep in introns and ect.). In addition, the next generation sequencing approach applied to a laboratory design of the USH-exome and deveped LSDBs USH-bases is freely available that records more than 2000 genotyped USH patients. In addition, comprehensive approach and multi-step strategy will be used for candidate genes and genetic modifiers testing (P5).