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: 10020018
• 负责人: Wadih Zein
• 金额: $ 23.68万
• 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/10020018
• 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 screening method; 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; Retina; Retinitis Pigmentosa; Severities; Site; Speech Intelligibility; Syndrome; Testing; Tropicamide; Tympanometry; United States National Institutes of Health; Universities; Usher Syndrome; Usher Syndrome, Type 1C; Usher Syndrome, Type 2A; 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; hearing impairment; macula; 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.

该研究涉及第一次眼科检查和视觉功能评估、听力和前庭评估，以及用于分子（DNA/基因分型）测试目的的血液样本。 眼部检查包括评估： 明显屈光的最佳矫正视力 裂隙灯检查和晶状体混浊拍照（如果有） 视野检查（戈德曼视野） 散瞳检眼镜检查（2.5%去氧肾上腺素和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，则进行荧光素血管造影/眼相干断层扫描。 使用以下一系列测试来评估听觉功能： 空气传导和骨传导的纯音阈值为 125-8000 Hz。 语音识别阈值 文字识别能力 鼓室导抗测试 中耳肌肉反射评估 失真产物耳声发射 (DPOAE) 阈值均衡噪声测试（十） 使用以下程序评估前庭功能： 一系列视频眼震检查测试，包括 (a) 动眼神经测试，(b) 自发、体位和体位测试，以及 (c) 热量刺激 转椅眼球运动 前庭肌源性诱发电位 (VEMP) 计算机化动态平台姿势描记术 (CDPP) 共有 249 名参与者参加了这项研究，累积上限为 400 名（200 名受影响的参与者和 200 名未受影响的参与者）。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城市大学 (CUNY) 皇后学院注册。目前共有 153 名受影响的参与者和 96 名未受影响的参与者注册。 已经对一些基因型进行了基因型-表型相关性。与其他 Usher I 型患者相比，PCDH15 R245X 突变纯合的 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，视力下降且视野​​收缩与年龄相关。以前未对 Usher 患者进行过的计算机动态姿势描记术提供了有关两种类型综合征前庭功能的新信息，并且可能是这些患者康复的有用工具。