Clinical Analysis Of Disorders Of Hearing And Balance

听力和平衡障碍的临床分析

• 批准号: 7299398
• 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/7299398
• 关键词: Clinical; Analysis; Disorders; Hearing; Balance

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. We are using pure-tone audiometry in a large cohort of monozygotic and dizygotic twins, 50 years of age or older, to estimate the proportion of age-related hearing loss (presbycusis) that is due to genetic factors. We have completed the first pilot phase of this study and are currently analyzing our zygosity test and audiometric test results. This is an important study since the results will determine whether it will be fruitful to search for genetic determinants of presbycusis or whether our public health and education efforts should be more focused on prevention of exposure to ototoxic agents such as loud noise. 2. In collaboration with Dr. Drayna of the Laboratory of Molecular Genetics, our audiology unit used a battery of audiologic tests to detect auditory physiologic abnormalities associated with tune deafness. They identified at least one test in which performance is strongly correlated with tune deafness. The study is completed and a manuscript is being prepared for submission for publication. 3. 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. 4. 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. 5. In collaboration with investigators from other NIH institutes, we continue to evaluate hearing and balance manifestations in 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. Tsilou, 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). 6. In collaboration with Dr. Goldbach-Mansky, the audiology unit characterized hearing and balance status in NOMID patients undergoing a clinical therapeutic trial of interleukin-1 beta inhibition. They found there was neither a positive nor negative effect on hearing during or after treatment. 7. The Audiology Unit completed an analysis of 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. 9. We ascertained a large North American family segregating progressive, nonsyndromic sensorineural hearing loss in a matrilineal/maternal/mitochondrial pattern of inheritance. The hearing loss phenotype is remarkable for its high degree of penetrance, early onset and rapid progression, and numerous anecdotal reports of sudden drops of hearing associated with head trauma.

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.我们在一个50岁或以上的单卵双胞胎和双卵双胞胎的大队列中使用纯音测听来估计由遗传因素引起的年龄相关性听力损失（老年性耳聋）的比例。我们已经完成了这项研究的第一个试点阶段，目前正在分析我们的接合性测试和听力测试结果。这是一项重要的研究，因为研究结果将决定寻找老年性耳聋的遗传决定因素是否富有成效，或者我们的公共卫生和教育工作是否应该更加注重预防暴露于耳毒性物质，如噪音。 2.在分子遗传学实验室的德雷纳博士的合作下，我们的听力学单位使用了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。他们确定了至少一项测试，其中表现与曲调耳聋密切相关。这项研究已经完成，目前正在编写一份手稿，以便提交出版。 3.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。 4.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。 5.在与其他国家卫生研究院研究人员的合作中，我们继续评估特纳综合征的听力和平衡表现（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. Tsilou，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）。 6.与Goldbach-Mansky博士合作，听力学单位对接受白细胞介素-1 β抑制临床治疗试验的NOMID患者的听力和平衡状态进行了表征。他们发现，在治疗期间或治疗后，对听力既没有积极也没有消极的影响。 7.听力学单位完成了一个大家族的8名受影响成员的临床表型分析，该家族分离常染色体显性遗传、非综合征型、舌后发作、进行性感音神经性听力损失，由DFNA 10位点的EYA 4基因突变引起。 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。 9.我们确定了一个大的北美家庭分离进行性，非综合征感音神经性听力损失的母系/母亲/线粒体遗传模式。听力损失表型以其高度隐匿性、早期发作和快速进展以及大量与头部创伤相关的听力突然下降的轶事报道而引人注目。