Clinical evidence for dystrophin dysfunction as a cause of hearing loss in locus DFN4.
Clinical evidence for dystrophin dysfunction as a cause of hearing loss in locus DFN4.
复制标题
抗肌营养不良蛋白功能障碍是 DFN4 位点听力损失原因的临床证据。
DOI：
10.1097/00005537-199905000-00010
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Lalwani,AK
中科院分区：
文献类型：
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作者：
Pfister,MH;Apaydin,F;Turan,O;Bereketoglu,M;Bilgen,V;Braendle,U;Kose,S;Zenner,HP;Lalwani,AK
目的：基因座DFN4是一个X连锁的非综合征性听力损失基因座，最初定位于Xp21.2。最近，我们将来自土耳其的第二个家庭的耳聋定位到同一地区，将其定位到杜氏肌营养不良（DMD）基因座内。本研究的目的是通过全面的听庭测试和高分辨率颞骨计算机断层扫描来表征土耳其家族的临床表型。方法：对一个三代家庭的14名成员进行了详细的研究，其中包括两名失聪男性。家庭成员接受了一般的身体和耳科检查、前庭测试、纯音听力学、耳声发射和阻抗测试。患者接受了颞骨高分辨率计算机断层扫描、视网膜电图（ERG）、肌电图、神经电图和血清肌酐磷酸激酶水平的测定。结果：男性先天性耳聋，前庭功能正常。携带者女性表现出轻度感音神经性听力损失，影响所有频率，没有耳声发射。3岁女童的耳声发射正常。在一个受影响的男性，ERG显示亚正常的暗位b波，通常见于DMD。颞骨电脑断层扫描正常。除了ERG发现外，没有DMD或贝克肌营养不良症（BMD）的临床或实验室证据。结论：土耳其家族的ERG异常以及DFN4位点在DMD内的定位强烈表明，肌营养不良蛋白的缺陷是导致该家族听力损失的原因。DMD和BMD患者应系统筛查感音神经性听力损失。这个家族为细胞骨架蛋白在正常听力中的关键作用提供了额外的证据。
Objective: Locus DFN4 is an X‐linked nonsyndromic hearing loss locus originally mapped to Xp21.2. Recently, we have mapped deafness in a second family from Turkey to the same region, refining the location to within the Duchenne muscular dystrophy (DMD) locus. The objective of this study was to characterize the clinical phenotype of the Turkish family with comprehensive audiovestibular testing and high‐resolution temporal bone computerized tomography.Methods: Fourteen members of a three‐generation family were studied in detail including two deaf affected males. Members of the family underwent general physical and otologic examination, vestibular testing, pure‐tone audiometry, otoacoustic emissions, and immitance testing. An affected male underwent high‐resolution computerized tomography of the temporal bone, electroretinogram (ERG), electromyography, electroneurography, and determination of serum creatinine phosphokinase level.Results: Affected males were congenitally deaf with normal vestibular function. Carrier females showed a mild sensorineural hearing loss affecting all frequencies and absent otoacoustic emissions. Otoacoustic emissions in a younger, 3‐year‐old carrier girl were normal. In an affected male, ERG demonstrated subnormal scotopic b‐wave typically seen in DMD. Computerized tomography of the temporal bone was normal. With the exception of the ERG finding, there was no clinical or laboratory evidence of DMD or Becker muscular dystrophy (BMD).Conclusion: The abnormal ERG in the Turkish family in conjunction with mapping of the DFN4 locus to within DMD strongly suggests that a defect in dystrophin is responsible for the hearing loss in this family. Patients with DMD and BMD should be screened systematically for sensorineural hearing loss. This family provides additional evidence for the critical role of cytoskeletal proteins in normal hearing.