Clinical Analysis Of Disorders Of Hearing And Balance

1.在与SHG的莫雷尔和弗里德曼博士的合作下，我们的听力学部门在一大批同卵和异卵双胞胎中使用了一系列中央听觉和语音处理测试，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，他们确定至少其中一项测试的表现显示出非常高的遗传率。这一特殊的特征可能适用于分子遗传学方法来识别导致观察到的变异的基因。 2.我们在一大群50岁或以上的同卵和异卵双胞胎中使用纯音测听，以估计遗传因素导致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合子测试和听力测试结果。这是一项重要的研究，因为结果将决定寻找老年性耳聋的遗传决定因素是否会有成果，或者我们的公共卫生和教育工作是否应该更多地侧重于预防接触耳毒性物质，如噪音。 2.与分子遗传学实验室的德雷纳博士合作，我们的听力学部门使用了一系列听力学测试，以检测与调音性耳聋相关的听觉生理异常。他们确定了至少一项测试，在这些测试中，表现与调音性耳聋密切相关。这项研究已经完成，目前正在编写一份手稿，准备提交出版。 3.听力学股与Al Braun博士和其他人合作，参与设计、实施和数据分析在接受多次核磁共振扫描或在新扫描仪中进行核磁共振扫描后对听觉系统(和听力)进行的安全研究。 4.听力科对听力损失和前庭导水管扩大的患者及其兄弟姐妹和父母进行听觉表型评估。目前已确定约90个先证者及其家系，听力学数据揭示了听觉表型与潜在的SLC26A4(PDS)基因的相关性。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.与其他NIH研究所的研究人员合作，我们继续评估Turner综合征(Bondy博士，NICHD)、Fanconi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症性疾病(Goldbach-Mansky博士，NIAMS)、家族性寒冷性荨麻疹/MuckleWells综合征(Goldbach-Mansky博士，NIAMS)、Fabry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(Tsilou博士，NIAMS)、家族性寒冷性荨麻疹/MuckleWells综合征(Goldbach-Mansky博士，NIAMS)、Fabry病(Dr.Schiffman，NINDS)、Pallister-Hall综合征(Dr.Biesecker，NHGRI)、Smith-Magenis综合征(Dr.Tsilou，NEI)、小猪皮癣(Dr.Kraemer，NIAMS)、法布里病(Dr.Schiffman，NINDS)、帕利斯特-霍尔综合征(Dr.Biesecker，NHGRI)、史密斯综合征(Dr.Tsilou，NIAI)、小猪皮癣(Dr.Kraemer，NCI)、法布里病(Dr.Schiffman，NINDS)、帕利斯特-霍尔综合征(Dr.Biesecker，NHGRI)、史密斯综合征(Dr.Tsilou，NIAMS)早衰症(戈登博士，NHGRI)、麦库恩-奥尔布赖特综合征和多发性骨质增生症纤维发育不良(柯林斯博士，NIDCR)和炭疽病(赖特博士，NIAID)。 6.听力学单位与Goldbach-Mansky博士合作，对接受白介素1β抑制临床治疗试验的NOMID患者的听力和平衡状况进行了研究。他们发现，在治疗期间或治疗后，这对听力既没有积极的影响，也没有消极的影响。 7.听力学单位完成了对一个大家庭中8名受影响成员的临床表型的分析，该大家庭分离出由DFNA10基因突变引起的常染色体显性、非综合征型、语后起病、进行性感音神经性听力损失。 8.听力学单位与利奥波德博士(NIMH)合作，参与设计、实施和分析暴露在功能性核磁共振噪声中的猕猴听觉系统的安全性研究。 9.我们确定了一个北美大家族，以母系/母系/线粒体遗传模式分离进行性、非综合征性感音神经性耳聋。听力损失的表型以其高度外显性、起病早、进展快和大量与头部创伤有关的听力突然下降的轶事报道而引人注目。

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.