目的了解及探讨OTOF基因突变的听神经病听障儿童植入人工耳蜗的术后康复效果。方法比较3例OTOF突变听神经病听障儿童人工耳蜗植入前后不同时期助听听阈、听觉言语评估(声母、韵母、双音节词、短句)及语言能力(理解能力、交流能力)的差异...目的了解及探讨OTOF基因突变的听神经病听障儿童植入人工耳蜗的术后康复效果。方法比较3例OTOF突变听神经病听障儿童人工耳蜗植入前后不同时期助听听阈、听觉言语评估(声母、韵母、双音节词、短句)及语言能力(理解能力、交流能力)的差异,探讨术后康复效果。结果3例患者术前平均助听听阈分别为50 dB HL、>85 dB HL、>69 dB HL,术后4个月分别为32 dB HL、36 dB HL、43 dB HL,术后12个月分别为29 dB HL、29 dB HL、35 dB HL;3例患者术前平均言语识别率分别为20.3%、20.5%、25.8%,术后4个月分别为36.5%、35.3%、48.8%,术后12个月分别为68.0%、31.3%、87.5%;3例患者术前平均语言能力分别为0.5岁、0岁、1.5岁,术后4个月分别为0岁、0岁、0.5岁水平,术后12月分别为2岁、2岁、3岁水平。结论OTOF突变的听神经病患儿植入人工耳蜗术后,随着康复时间的延长可获得不同程度的康复效果,其个体差异较大。展开更多
Objective: Congenital auditory neuropathy(AN) affects hearing and speech development. The degree of hearing difficulty in congenital AN varies as a function of pathology at the inner ear hair cell(IHC) synapses or the...Objective: Congenital auditory neuropathy(AN) affects hearing and speech development. The degree of hearing difficulty in congenital AN varies as a function of pathology at the inner ear hair cell(IHC) synapses or the auditory nerve. We report a case of a Chinese girl with AN revealed by OTOF(otoferlin) gene mutation analysis who had only a mild hearing loss.Patient: A 13-year-old Chinese girl was diagnosed as having congenital AN on the basis of OTOF gene mutation analysis. She manifest a mild sensorineural hearing loss with 50% maximum monosyllable speech discrimination rate, normal DPOAEs(distortion product otoacoustic emissions) beyond ambient noise levels, only SPs(summating potentials) evoked during ECoG(electrocochleography) and absent ABRs(auditory evoked brainstem responses) bilaterally to clicks presented at 100 d Bn HL. She was able to effectively communicate with others by speech reading owing to her mild hearing loss. Moreover, bilateral hearing aids helped her to communicate.Conclusions: Our patient was demonstrated to have a mutation on the OTOF gene. Nevertheless, she was able to communicate using auditory visual speech reading in spite of a mild auditory threshold elevation probably due to partial pathology at the IHC synapses or in the auditory nerve.展开更多
目的:对比2015年美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)和分子病理学会(Association for Molecular Pathology,AMP)发布的变异解读标准与指南(本文中简称2015 ACMG/AMP指南)与2018年...目的:对比2015年美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)和分子病理学会(Association for Molecular Pathology,AMP)发布的变异解读标准与指南(本文中简称2015 ACMG/AMP指南)与2018年临床基因组资源中心(Clinical Genome Resource,ClinGen)耳聋专病小组针对遗传性听力损失(hearing loss,HL)发布的变异解读指南专家规范(本文中简称2018HL专病指南)在评估听神经病患者OTOF基因变异致病性中的异同。方法:以38例OTOF基因变异听神经病患者作为研究对象(男23例、女15例,年龄范围0.3~25.9岁),经全基因组重测序、全外显子组测序或目标区域靶向(Panel)测序结合一代Sanger测序验证,38例听神经病患者均检出携带两个以上OTOF变异位点,共计59个候选位点,分别使用2015ACMG/AMP指南以及2018HL专病指南对其致病性进行判断。与2015年指南判断结果相比,2018年指南判断的致病性等级更强定义为升级,更弱定义为降级。采用SPSS 20.0软件进行统计学分析。结果:2015 ACMG/AMP指南和2018 HL专病指南的变异分类一致率为72.9%(43/59)。致病性升级变异位点占13.6%(8/59),致病性降级变异位点占13.6%(8/59)。两指南致病性判定不一致主要集中在PVS1、PM3、PP2、PP3以及PP5等级证据的应用上。剪接变异、错义变异、框内插入/缺失以及同义变异致病性分布发生改变,其中剪接变异改变差异具有统计学意义(P=0.013)。结论:针对听神经病患者OTOF基因变异进行致病性判断时,2018HL专病指南与2015ACMG/AMP指南存在不一致,2018HL专病指南对证据进行删减及进一步细分,打破常规对于变异类型的固化思维,使得致病性分级更有迹可循,提高可信度。展开更多
The pathogenic factors of deafness are complex;more than 50%of cases are caused by genetic factors.Between 75%and 80%of cases of hereditary hearing impairment are autosomal recessive,15%to 25%are autosomal dominant,an...The pathogenic factors of deafness are complex;more than 50%of cases are caused by genetic factors.Between 75%and 80%of cases of hereditary hearing impairment are autosomal recessive,15%to 25%are autosomal dominant,and 1%to 2%are mitochondrial or X-linked.Cochlea implantation is the main method for treating severe and extremely severe bilateral sensorineural deafness and it is widely used in clinical treatment.As clinical cases of cochlea implantation accumulate,differences in the efficacy of implantation in individuals are emerging and attracting attention.In addition to residual hearing level,implantation age,and other factors,gene mutation is an important factor influencing postoperative rehabilitation in patients.With continuous progress in genetic testing technology for deafness,genetic diagnosis has become an important tool in preoperative evaluation and postoperative effect prediction in patients undergoing cochlear implantation.This article reviews the current status and future development of cochlear implantation in the treatment of hereditary deafness resulting from mutations in common deafness-causing genes.展开更多
文摘目的了解及探讨OTOF基因突变的听神经病听障儿童植入人工耳蜗的术后康复效果。方法比较3例OTOF突变听神经病听障儿童人工耳蜗植入前后不同时期助听听阈、听觉言语评估(声母、韵母、双音节词、短句)及语言能力(理解能力、交流能力)的差异,探讨术后康复效果。结果3例患者术前平均助听听阈分别为50 dB HL、>85 dB HL、>69 dB HL,术后4个月分别为32 dB HL、36 dB HL、43 dB HL,术后12个月分别为29 dB HL、29 dB HL、35 dB HL;3例患者术前平均言语识别率分别为20.3%、20.5%、25.8%,术后4个月分别为36.5%、35.3%、48.8%,术后12个月分别为68.0%、31.3%、87.5%;3例患者术前平均语言能力分别为0.5岁、0岁、1.5岁,术后4个月分别为0岁、0岁、0.5岁水平,术后12月分别为2岁、2岁、3岁水平。结论OTOF突变的听神经病患儿植入人工耳蜗术后,随着康复时间的延长可获得不同程度的康复效果,其个体差异较大。
文摘Objective: Congenital auditory neuropathy(AN) affects hearing and speech development. The degree of hearing difficulty in congenital AN varies as a function of pathology at the inner ear hair cell(IHC) synapses or the auditory nerve. We report a case of a Chinese girl with AN revealed by OTOF(otoferlin) gene mutation analysis who had only a mild hearing loss.Patient: A 13-year-old Chinese girl was diagnosed as having congenital AN on the basis of OTOF gene mutation analysis. She manifest a mild sensorineural hearing loss with 50% maximum monosyllable speech discrimination rate, normal DPOAEs(distortion product otoacoustic emissions) beyond ambient noise levels, only SPs(summating potentials) evoked during ECoG(electrocochleography) and absent ABRs(auditory evoked brainstem responses) bilaterally to clicks presented at 100 d Bn HL. She was able to effectively communicate with others by speech reading owing to her mild hearing loss. Moreover, bilateral hearing aids helped her to communicate.Conclusions: Our patient was demonstrated to have a mutation on the OTOF gene. Nevertheless, she was able to communicate using auditory visual speech reading in spite of a mild auditory threshold elevation probably due to partial pathology at the IHC synapses or in the auditory nerve.
文摘目的:对比2015年美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)和分子病理学会(Association for Molecular Pathology,AMP)发布的变异解读标准与指南(本文中简称2015 ACMG/AMP指南)与2018年临床基因组资源中心(Clinical Genome Resource,ClinGen)耳聋专病小组针对遗传性听力损失(hearing loss,HL)发布的变异解读指南专家规范(本文中简称2018HL专病指南)在评估听神经病患者OTOF基因变异致病性中的异同。方法:以38例OTOF基因变异听神经病患者作为研究对象(男23例、女15例,年龄范围0.3~25.9岁),经全基因组重测序、全外显子组测序或目标区域靶向(Panel)测序结合一代Sanger测序验证,38例听神经病患者均检出携带两个以上OTOF变异位点,共计59个候选位点,分别使用2015ACMG/AMP指南以及2018HL专病指南对其致病性进行判断。与2015年指南判断结果相比,2018年指南判断的致病性等级更强定义为升级,更弱定义为降级。采用SPSS 20.0软件进行统计学分析。结果:2015 ACMG/AMP指南和2018 HL专病指南的变异分类一致率为72.9%(43/59)。致病性升级变异位点占13.6%(8/59),致病性降级变异位点占13.6%(8/59)。两指南致病性判定不一致主要集中在PVS1、PM3、PP2、PP3以及PP5等级证据的应用上。剪接变异、错义变异、框内插入/缺失以及同义变异致病性分布发生改变,其中剪接变异改变差异具有统计学意义(P=0.013)。结论:针对听神经病患者OTOF基因变异进行致病性判断时,2018HL专病指南与2015ACMG/AMP指南存在不一致,2018HL专病指南对证据进行删减及进一步细分,打破常规对于变异类型的固化思维,使得致病性分级更有迹可循,提高可信度。
文摘The pathogenic factors of deafness are complex;more than 50%of cases are caused by genetic factors.Between 75%and 80%of cases of hereditary hearing impairment are autosomal recessive,15%to 25%are autosomal dominant,and 1%to 2%are mitochondrial or X-linked.Cochlea implantation is the main method for treating severe and extremely severe bilateral sensorineural deafness and it is widely used in clinical treatment.As clinical cases of cochlea implantation accumulate,differences in the efficacy of implantation in individuals are emerging and attracting attention.In addition to residual hearing level,implantation age,and other factors,gene mutation is an important factor influencing postoperative rehabilitation in patients.With continuous progress in genetic testing technology for deafness,genetic diagnosis has become an important tool in preoperative evaluation and postoperative effect prediction in patients undergoing cochlear implantation.This article reviews the current status and future development of cochlear implantation in the treatment of hereditary deafness resulting from mutations in common deafness-causing genes.