Clinical Analysis Of Disorders Of Hearing And Balance

听力和平衡障碍的临床分析

• 批准号: 7130266
• 负责人: Andrew J Griffith
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
• 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/7130266
• 关键词: Fabry' s disease; Macaca; Smith Magenis syndrome; Turner' s syndrome; Usher syndrome; Von Hippel Lindau syndrome; auditory pathways; balance; bone marrow disorder; clinical research; congenital aplastic anemia; deafness; diagnosis design /evaluation; diagnosis procedure safety; family genetics; genetic disorder; hearing disorders; hearing tests; human subject; magnetic resonance imaging; medical complication; neurogenetics; neuromuscular disorder; phenotype; transcranial magnetic stimulation; twin /multiplet; vestibular apparatus

1. In collaboration with Drs. Morell and Friedman of the SHG, our audiology unit has used a battery of tests of central auditory and speech processing in a large cohort of monozygotic and dizygotic twins in order to test the hypothesis that one or more measurable parameters of these phenomena are heritable, They have determined that performance on at least one of the tests shows a very high heritability. This particular trait may be amenable to molecular genetic approaches to identify the genes underlying the observed variation. 2. In collaboration with Dr. Drayna of the Laboratory of Molecular Genetics, our audiology unit is using a battery of audiologic tests to detect auditory physiologic abnormalities associated with tune deafness. They have identified at least one test in which performance is strongly correlated with tune deafness. 3. In collaboration with Drs. Hallett and Garvey of the NINDS, the audiology unit has been involved in the design, implementation, and data analysis for two different safety studies on the auditory system (and hearing) after exposure to transcranial magnetic stimulation (TMS) in adults and children, respectively. TMS is a widely utilized clinical neurophysiologic technique whose effects on hearing have not been adequately characterized for many of the devices, or for children. 4. In collaboration with Dr. Al Braun and others, the audiology unit is involved in the design, implementation, and data analysis of safety studies on the auditory system (and hearing) after exposure to either multiple MRI scans, or MRI scans performed in new scanners. 5. The Hearing Section conducts the auditory phenotypic assessment of individuals with hearing loss and enlarged vestibular aqueducts (EVA), as well as their siblings and parents. About 90 probands and their families have now been ascertained, and the audiologic data reveals a correlation of the auditory phenotype with the underlying SLC26A4 (PDS) genotype. The audiology unit is currently evaluating details of the auditory phenotype to search for features that predict genotype, clinical prognosis, or clinical diagnosis. 6. In collaboration with investigators from other NIH institutes, we continue to evaluate hearing and balance manifestations in Von Hippel-Landau disease (Dr. Linehan, NCI), Turner syndrome (Dr. Bondy, NICHD), Fanconi anemia and other inherited bone marrow failure syndromes (Dr. Alter), neonatal onset multi-system inflammatory disorder (Dr. Goldbach-Mansky, NIAMS), familial cold urticaria/MuckleWells syndrome (Dr. Goldbach-Mansky, NIAMS), Fabry disease (Dr. Schiffman, NINDS), Pallister-Hall syndrome (Dr. Biesecker, NHGRI), Smith-Magenis syndrome (Ms. Smith, NHGRI), Usher syndrome (Dr. Sieving, NEI), xeroderma pigmentosum (Dr. Kraemer, NCI), progeria (Dr. Gordon, NHGRI), McCune-Albright syndrome and Polyostotic Fibrous Dysplasia (Dr. Collins, NIDCR), and anthrax (Dr. Wright, NIAID). 7. The Audiology Unit has characterized the clinical phenotype of eight affected members of a large family segregating autosomal dominant, nonsyndromic, postlingual-onset, progressive sensorineural hearing loss caused by a mutation of the EYA4 gene at the DFNA10 locus. 8. In collaboration with Dr. Leopold (NIMH), the audiology unit is involved in the design, implementation, an analysis of safety studies on the auditory system in macaque monkeys exposed to functional MRI noise.

1.在与SHG的Morell和Friedman博士的合作中，我们的听力学单位在一大批同卵双胞胎和异卵双胞胎中使用了一组中央听觉和语言处理测试，以测试这些现象的一个或多个可测量参数是可遗传的假设，他们已经确定至少一个测试的表现显示出非常高的遗传性。这种特殊的性状可能是服从分子遗传学方法，以确定所观察到的变化的基因。 2.在分子遗传学实验室的德雷纳博士的合作下，我们的听力学单位正在使用一系列听力学测试来检测与音调性耳聋相关的听觉生理异常。他们已经确定了至少一项测试，其中表现与曲调耳聋密切相关。 3.与NINDS的Hallett和Garvey博士合作，听力学部门参与了两项不同的安全性研究的设计，实施和数据分析，这些研究分别针对成人和儿童暴露于经颅磁刺激（TMS）后的听觉系统（和听力）。TMS是一种广泛使用的临床神经生理学技术，其对许多器械或儿童听力的影响尚未得到充分表征。 4.与Al Braun博士和其他人合作，听力学部门参与了多次MRI扫描或在新扫描仪中进行MRI扫描后听觉系统（和听力）安全性研究的设计、实施和数据分析。 5.听力科对听力损失和前庭水管扩大（伊娃）的个体及其兄弟姐妹和父母进行听觉表型评估。现已确定了约90个先证者及其家系，听力学数据揭示了听觉表型与潜在SLC 26 A4（PDS）基因型的相关性。听力学单位目前正在评估听觉表型的细节，以寻找预测基因型、临床预后或临床诊断的特征。 6.在与其他国家卫生研究院研究人员的合作中，我们继续评估Von Hippel-Landau病的听力和平衡表现（Linehan博士，NCI），特纳综合征（邦迪博士，NICHD），范可尼贫血和其他遗传性骨髓衰竭综合征（Dr. Alter），新生儿发作性多系统炎性疾病（Goldbach-Mansky博士，NIAMS），家族性寒冷性荨麻疹/MuckleWells综合征（Goldbach-Mansky博士，NIAMS），法布里病（Schiffman博士，NINDS），Pallister-Hall综合征（Biesecker博士，NHGRI），Smith-Magenis综合征（Smith女士，NHGRI），Usher综合征（Dr. Sieving，NEI），着色性干皮病（Dr. Kraemer，NCI）、早衰症（Dr. Gordon，NHGRI）、McCune-Albright综合征和多发性纤维增生异常（Dr.柯林斯，NIDCR）和炭疽（Dr. Wright，NIAID）。 7.听力学单位的特点是一个大家庭的8个受影响的成员分离常染色体显性，非综合征，舌后发病，进行性感音神经性听力损失引起的突变EYA 4基因在DFNA 10位点的临床表型。 8.与Leopold博士（NIMH）合作，听力学部门参与了对暴露于功能性MRI噪声的猕猴听觉系统的安全性研究的设计，实施和分析。