Clinical and Genetic Testing of Patients With Usher Syndrome

This study is aimed to characterize Russian population of Usher patients.

Tasks:

Stage 1. Formation of the primary cohort of patients. Patients pre-recruiting will be performed based on Deaf-Blind Support Foundation "Con-nection" patient database analysis. Patients with clinically confirmed Usher syndrome will be evaluated according to available data of the clinical examination.

Stage 2. Clinical examination of patients.

Each patient will undergo the following diagnostic procedures according to the unified protocol:

* Visometry (with correction and without correction)
* Ophthalmoscopy
* Perimetry
* Optical coherence tomography
* Electroretinography
* Visually evoked potentials
* Refractometry
* Pneumotonometry
* Biomicroscopy
* Tonal audiometry
* Electronic audiometry (ASSR test)
* Acoustic impedance measurement
* Vestibulometry
* Electronystagmography
* Any additional examinations and consultations if necessary

Medical record will be developed and maintained for each patient consisting results of extended clinical examination.

Stage 3. Genetic study of patients. All enrolled patients will undergo single 4 ml peripheral venous blood sampling. DNA will be extracted from leucocytes. DNA samples will be analyzed and placed for long-term storage in liquid nitrogen. Statistical and bioinformatic analysis of detected genetic mutations in the study cohort will be performed.

Primary outcomes

• Changes in visual acuity [Up to 4 weeks]: Measured by visometry
• Changes in structures of fundus of the eye-1 [Up to 4 weeks]: Measured by ophthalmoscopy
• Changes in structures of fundus of the eye-2 [Up to 4 weeks]: Measured by optical coherence tomography
• Changes in visual field [Up to 4 weeks]: Measured by perimetry
• Changes in retinal ganglion cell dysfunction [Up to 4 weeks]: Measured by electroretinography
• Changes in brain visual cortex neural pathways [Up to 4 weeks]: Measured by visually evoked potentials
• Changes in optical refraction [Up to 4 weeks]: Measured by refractometry
• Changes in intraocular pressure [Up to 4 weeks]: Measured by pneumotonometry
• Changes in the lens, cornea, anterior segment of the eye [Up to 4 weeks]: Measured by biomicroscopy
• Changes in hearing-1 [Up to 4 weeks]: Measured by tonal audiometry
• Changes in hearing-2 [Up to 4 weeks]: Measured by electronic audiometry (ASSR test)
• Changes in efficient sound transmission in the middle ear [Up to 4 weeks]: Measured by acoustic impedance measurement
• Changes in vestibular functions [Up to 4 weeks]: Measured by vestibulometry
• Changes in vestibular reactions [Up to 4 weeks]: Measured by electronystagmography

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Patient fulfill the clinical characteristics for Usher syndrome type I, II or III as defined by the Usher syndrome consortium
* According to the results of audiometry, hearing loss is moderate or severe (level of acoustic threshold of audibility is 41 decibel and higher).
* Results of perimetry for each eye show narrowing for 15 degrees or more.
* Patient is familiar with Participant information sheet
* Patient signed informed consent form

Non-inclusion Criteria:

* Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion
* Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.)
* Medical history of traumatic injury of eyes, barotrauma, concussion, craniocerebral trauma, cerebrovascular accident

Exclusion Criteria:

* Patient's refusal from the further participation in the trial
* Decompensated diabetes mellitus
* Severe coronary artery disease
* Chronic infectious disease
* Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy

• Results publication: Ivanova ME, Trubilin VN, Atarshchikov DS, Demchinsky AM, Strelnikov VV, Tanas AS, Orlova OM, Machalov AS, Overchenko KV, Markova TV, Golenkova DM, Anoshkin KI, Volodin IV, Zaletaev DV, Pulin AA, Nadelyaeva II, Kalinkin AI, Barh D. Genetic screening of Russian Usher syndrome patients toward selection for gene therapy. Ophthalmic Genet. 2018 Dec;39(6):706-713. doi: 10.1080/13816810.2018.1532527. Epub 2018 Oct 25. PMID 30358468

• Vladimir N Trubilin, MD, PhD, Prof, Principal investigator, State Research Center Burnasyan Federal Medical Biophysical Center Federal Medical-Biological Agency