Natural History and Genetic Studies of Usher Syndrome

亚瑟综合症的自然史和遗传学研究

• 批准号: 10266900
• 负责人: Wadih Zein
• 金额: $ 23.4万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10266900
• 关键词: 10q; 11p; 11q; 17q; Affect; Air; Auditory; Blood specimen; Bone Conduction; CDH23 gene; Categories; Chromosomes; Cities; Clinical; DNA; Disease; Electroretinography; Enrollment; Equilibrium; Evaluation; Eye Movements; Fluorescein Angiography; Fundus photography; Genes; Genetic study; Genotype; Inherited; Knowledge; Lens Opacities; Life; Link; MYO7A gene; Molecular; Molecular Genetics; Mutation; Natural History; Nature; New York; Night Blindness; Noise; Ophthalmoscopes; Optic Nerve; PCDH15 gene; Participant; Patients; Phenotype; Phenylephrine; Photography; Positioning Attribute; Procedures; Protocols documentation; Reflex action; Rehabilitation therapy; Reporting; Rest; Retinal macula; Retinitis Pigmentosa; Severities; Site; Speech Intelligibility; Syndrome; Testing; Tropicamide; Tympanometry; USH1C gene; USH2A gene; United States National Institutes of Health; Universities; Usher Syndrome; Usher Syndrome Type 1; Usher Syndrome Type 2; VLGR1 gene; Vestibular Function Tests; Vision; Visit; Visual Acuity; Visual Fields; WHRN gene; age related; caloric stimulation; chromosome 5q loss; college; computerized; constriction; deaf; disease natural history; ear muscle; early childhood; genetic deafness; genetic testing; hearing impairment; macular edema; middle ear; oculomotor; otoacoustic emission; speech recognition; tomography; tool

The study involved a first visit with ocular exam and assessment of visual function, audiological and vestibular evaluation, and a blood sample for the purpose of molecular (DNA/genotyping) testing. The ocular examination included an assessment of: Best corrected visual acuity with manifest refraction A slit lamp examination and photography of lens opacity, if present Visual field examination (Goldmann visual field) Dilated ophthalmoscopic examination (2.5% phenylephrine and 1% tropicamide) Electroretinography (ERG) Fundus photography of retina, macula, and optic nerve Fluorescein angiography/ocular coherence tomography if macular edema is suspected. Auditory function were evaluated using the following battery of tests: Pure tone thresholds by air and bone conduction for 125-8000 Hz. Speech recognition threshold Word recognition ability Tympanometry Middle ear muscle reflex assessment Distortion product otoacoustic emissions (DPOAEs) Threshold equalizing noise test (TEN) Vestibular function were evaluated using the following procedures: A Videoonystagmography battery of tests including (a) oculomotor tests, (b) spontaneous, positional and positioning tests, and (c) caloric stimulation Rotary chair eye movements Vestibular evoked myogenic potentials (VEMP) Computerized dynamic platform posturography (CDPP) A total number of 249 participants have been enrolled in this study with an accrual ceiling of 400 (200 affected participants and 200 unaffected participants). A total of 237 participants have enrolled at NIH. A total of 12 participants have enrolled at the collaborative site, Queens College of the City University of New York (CUNY). There are currently a total of 153 affected and 96 unaffected participants enrolled. Genotype-phenotype correlations have been performed for some of the genotypes. Usher type I patients homozygous for the R245X mutation of PCDH15 appear to be severely affected from early in life when compared with the rest of Usher type I patients. In Usher type 2A patients, visual acuity decreased and visual field constriction was found to be age-dependent. Computerized dynamic posturography, not previously performed on Usher patients, has provided new information about the vestibular function of both types of the syndrome and might be a useful tool in the rehabilitation of these patients.

该研究包括首次就诊，进行眼部检查和视功能评估，听力学和前庭评估，以及用于分子（DNA/基因分型）检测的血液样本。 眼部检查包括以下评估： 最佳矫正视力与显性屈光 裂隙灯检查和透镜混浊照相（如存在） 视野检查（Goldmann视野） 散瞳检眼镜检查（2.5%苯乙双胍和1%托吡卡胺） 视网膜电图（ERG） 视网膜、黄斑和视神经的眼底摄影 如果怀疑黄斑水肿，则进行血管造影/眼相干断层扫描。 使用以下成套测试评价听觉功能： 125-8000 Hz空气和骨传导的纯音阈值。 言语识别阈 认字能力 鼓室测压 中耳肌肉反射评估 畸变产物耳声发射 阈值均衡噪声测试（TEN） 使用以下程序评价前庭功能： 一组视频眼震描记术试验，包括（a）眼球运动试验，（B）自发、位置和定位试验，和（c）热刺激 旋转椅眼动 前庭诱发肌源性电位（VEMP） 计算机动态平台姿势描记术（CDPP） 本研究共入组了249例受试者，累积上限为400例（200例受影响受试者和200例未受影响受试者）。共有237名参与者在NIH注册。共有12名参与者在合作地点-纽约皇后学院注册。目前共有153名受影响的受试者和96名未受影响的受试者入组。 已经对一些基因型进行了基因型-表型相关。与其他Usher I型患者相比，PCDH 15的R245 X突变纯合子的Usher I型患者似乎从生命早期就受到严重影响。在Usher 2A型患者中，视力下降和视野收缩被发现是年龄依赖性的。计算机动态姿势描记术，以前没有进行Usher患者，提供了新的信息前庭功能的两种类型的综合征，并可能是一个有用的工具，在这些患者的康复。