ABSTRACT
Objectives@#. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. @*Methods@#. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. @*Results@#. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. @*Conclusion@#. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.
ABSTRACT
Objective To investigate the protective effects of the extract of ginkgo biloba(EGb)on the spiralganglion neuron(SGNs)in cochlea tissues on the hearing loss induced by noise in rats.Methods Thirty-six healthy animals were randomly divided into three groups:the normal control group(n=12).the noise exposured group(n =12)and the EGb treamment group(n=12).The control group received no noise and no medications.The other two groups were exposed to the noise of 110 dB SPL for consecutively 10 days,6 hours per day.The treatment group rats were injected with 10 ml/d EGb while the other two groups with 0.9%saline of the same amount.The experiment lasted for ten days.The rats were measured by auditory brainsterm response(ABR)before and after niose exposure.The ultrastructural changes of SGNs were detected by tranismision electron microscpoe(TEM) and the contents of malondiadehyde(MDA) and activities of superoxide dismutase(SOD)were also measured.Results Hearing were signifcantlly decreased in the experimental group.Nevertheless,EGb relatively reduced the contents of MDA while increased the activities of SOD.Conclusion EGb seems to be able to moderately pretect SGNs and to play a preventive and remedial role in noise-induced hearing loss.
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OBJECTIVE To investigate the effect of ischemic postcondioning on cochlea following cochlear ischemia-reperfusion injury in rats. METHODSForty two healthy male SD rats were randomly divided into 3 groups, namely, the sham operation control group, the ischemia reperfusion group and ischemic postcondinging group. There were 14 rats in each group. The content of molondialdehyde(MDA) as well as the activity of catalase(CAT)in cochlea was measured by histochemistry. The ultrastructural changes of stria vascularis capillaries of the cochlea in experimental rats were examined by transmission electron microscopy(TEM). RESULTS In the ischemia reperfusion group, the CAT activities were decreased and MDA concentrations were increased significantly compared with those in the control group. However, in the ischemic postcondinging group, the activities of CAT were increased and MDA concentrations were decreased compared with those in the ischemia reperfusion group. Moreover, lesions were detected in the stria vascularis capillaries in all the three groups. The capillaries of stria vascularis were injured severely in ischemia reperfusion group. In the ischemic postcondinging group, the damage of capillary of stria vascularis were reduced significantly compared with that in ischemia reperfusion group, the structures were near normal, and no obvious destruction was observed. COCLUSION Ischemic postconditioning may markedly reduce the excessive generation of oxygen free radical during the process of ischemia-reperfusion injury and might be a potential strategy for its therapy.