Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without he...Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genom- ic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 （35delG, 176del16bp, 235delC, 299delAT）, GJB3 （C538T） ,SLC26A4 （ IVS72A〉G, A2168G） and mito- chondrial DNA 12S rRNA （A1555G, C1494T） . Further genetic testing were provided to the spouses and newborns of the screened carriers. Results Peripheral blood of 430 pregnant women were detected, detection of deafness gene mutation carri- ers in 24 cases（4.2%）, including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took further genetic tests, and 6 newborns inherited the mutation from their mother. Conclusion The common deafness genes muta- tion has a high carrier rate in pregnant women group, 235delC and IVS7-2A〉G heterozygous mutations are common.展开更多
BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for...BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical.Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.CASE SUMMARY The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss.We learned from the patient’s medical history collection that multiple family members also had similar hearing loss,generally occurring around the age of 40.Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant.To provide evidence supporting that this variant is responsible for the hearing loss in the studied family,we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype.In addition,the clinical manifestation of the 11 affected family members was found to be lateonset bilateral slowly progressive hearing loss,inherited in this family in an autosomal dominant manner.None of the affected family members had visual impairment or vestibular symptoms;therefore,we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.CONCLUSION We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants,and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.展开更多
Hearing impairment is considered as the most prevalent impairment worldwide. Almost 600 million people in the world suffer from mild or moderate hearing impairment, an estimated 10% of the human population. Genetic fa...Hearing impairment is considered as the most prevalent impairment worldwide. Almost 600 million people in the world suffer from mild or moderate hearing impairment, an estimated 10% of the human population. Genetic factors play an important role in the pathogenesis of this disorder. Hereditary hearing loss is divided into syndromic hearing loss （associated with other anomalies） and non-syndromic hearing loss （not associated with other anomalies）. Approximately 80% of genetic deafness is non-syndromic. On the basis of the frequency of hearing loss, hereditary non-syndromic hearing loss can be divided into high-, mid-, low-, and total-frequency hearing loss. An audiometric finding of mid-frequency sensorineural hearing loss, or a ＂bowl-shaped＂ audiogram, is uncommon. Up to now, merely 7 loci have been linked to mid-frequency hearing loss. Only four genetic mid- frequency deafness genes, namely, DFNA10 （EYA4）, DFNA8/12 （TECTA）, DFNA13 （COLIIA2）, DFNA44 （CCDC50）, have been reported to date. This review summarizes the research progress of the four genes to draw attention to mid-frequency deafness genes.展开更多
目的 研究一个家系中2例非综合征型遗传性聋患者的致病原因。方法 收集该耳聋家系临床检查结果资料,采集静脉血后提取DNA,应用全外显子组测序技术分析可疑致病基因,并通过Sanger测序对变异进行验证。结果 该家系中2代5人,先证者(Ⅱ-2,9...目的 研究一个家系中2例非综合征型遗传性聋患者的致病原因。方法 收集该耳聋家系临床检查结果资料,采集静脉血后提取DNA,应用全外显子组测序技术分析可疑致病基因,并通过Sanger测序对变异进行验证。结果 该家系中2代5人,先证者(Ⅱ-2,9岁)和其弟弟(Ⅱ-3)均为迟发性感音神经性听力损失,患者父母听力正常。先证者弟弟(Ⅱ-3)携带相同突变位点。基因检测结果显示,先证者携带CDH23基因c.4762C>T(p.ARG1588TRP)和c.6604G>A(p.ASP2202ASN)。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics, ACMG)遗传变异分类标准与指南分析显示,c.4762C>T和c.6604G>A位点均为致病突变。蛋白功能分析发现,变异后氨基酸改变造成蛋白结构发生改变,进而影响蛋白质功能。结论 CDH23基因c.4762C>T和c.6604G>A复合杂合突变位点组合很可能是该家系耳聋致病基因。展开更多
In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmenta...In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.展开更多
目的分析陕西省宝鸡地区新生儿常见遗传性耳聋基因突变情况,为遗传性耳聋患者的临床治疗提供参考依据。方法选取2021年1月至2023年4月在陕西宝鸡市妇幼保健院出生的1985例新生儿作为研究对象,采用微阵列芯片杂交法检测4种遗传性耳聋基因...目的分析陕西省宝鸡地区新生儿常见遗传性耳聋基因突变情况,为遗传性耳聋患者的临床治疗提供参考依据。方法选取2021年1月至2023年4月在陕西宝鸡市妇幼保健院出生的1985例新生儿作为研究对象,采用微阵列芯片杂交法检测4种遗传性耳聋基因(GJB2、GJB3、SLC26A4和线粒体mt DNA 12S rRNA)15个位点,将耳聋基因检测结果进行统计分析。同时将陕西宝鸡地区新生儿耳聋基因突变情况与国内其他地区进行比较。结果1985例新生儿中检出耳聋基因突变108例(5.44%)其中GJB2携带率最高,为2.67%,SLC26A4携带率为2.02%,GJB3携带率为0.40%,线粒体mt DNA 12S rRNA携带率为0.35%;以GJB2(c.235 del C)突变率(1.86%)最高,其次为SLC26A4(c.IVS7-2 A>G)突变率(1.56%)。与国内其他地区比较,陕西宝鸡地区除线粒体mt DNA 12S rRNA(m.1555 A>G)突变率无差异外,GJB2(c.235 del C)、GJB3(c.538 C>T)、SLC26A4(c.IVS-27-2A>G)突变率均有差异。结论陕西宝鸡地区新生儿携带的耳聋基因突变以GJB2为主,该研究有助于及早查明该地区新生儿听力损失的病因,从而对遗传性耳聋患者进行早期干预。展开更多
目的分析枣庄市4129例孕妇常见耳聋基因突变位点筛查结果,探讨枣庄市孕期女性常见耳聋基因突变分布特点及耳聋基因筛查的临床意义。方法选取2020年10月至2022年4月就诊于枣庄市妇幼保健院进行耳聋基因筛查的4129例孕妇为研究对象,经知...目的分析枣庄市4129例孕妇常见耳聋基因突变位点筛查结果,探讨枣庄市孕期女性常见耳聋基因突变分布特点及耳聋基因筛查的临床意义。方法选取2020年10月至2022年4月就诊于枣庄市妇幼保健院进行耳聋基因筛查的4129例孕妇为研究对象,经知情同意后采集外周血,利用高通量测序法检测18个耳聋相关基因共100个突变位点,分析各突变位点的检出率及分布情况。对耳聋基因携带者孕妇的配偶进行基因测序,并对孕妇妊娠结局进行随访。结果在4129例受检者中,共检出311例携带耳聋基因突变,总体突变携带率为7.53%。其中,GJB2突变携带者140例(3.39%),SLC26A4突变携带者105例(2.54%),GJB3突变携带者21例(0.51%),线粒体12S rRNA突变携带者34例(0.82%),TMC1突变携带者1例(0.02%),纯合或复合杂合突变者4例(0.10%),双基因突变携带者6例(0.15%)。线粒体12S rRNA基因突变者均未出现听力缺失,其新生儿也均通过了听力筛查。结论在枣庄市孕期女性常见耳聋基因突变位点中,阳性检出率较高的3种变异分别是GJB2235 del C(2.47%)、SLC26A4 IVS7-2 A>G(1.24%)和GJB2299 del AT(0.63%)。线粒体12S rRNA基因突变者均未出现听力缺失,与目前临床对氨基糖苷类药物的控制使用有关。针对产前孕妇进行耳聋基因热点变异筛查,明确本地区耳聋基因突变的人群特点,对有效实现遗传性耳聋的二级预防具有重要意义。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Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genom- ic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 （35delG, 176del16bp, 235delC, 299delAT）, GJB3 （C538T） ,SLC26A4 （ IVS72A〉G, A2168G） and mito- chondrial DNA 12S rRNA （A1555G, C1494T） . Further genetic testing were provided to the spouses and newborns of the screened carriers. Results Peripheral blood of 430 pregnant women were detected, detection of deafness gene mutation carri- ers in 24 cases（4.2%）, including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took further genetic tests, and 6 newborns inherited the mutation from their mother. Conclusion The common deafness genes muta- tion has a high carrier rate in pregnant women group, 235delC and IVS7-2A〉G heterozygous mutations are common.
文摘BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical.Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.CASE SUMMARY The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss.We learned from the patient’s medical history collection that multiple family members also had similar hearing loss,generally occurring around the age of 40.Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant.To provide evidence supporting that this variant is responsible for the hearing loss in the studied family,we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype.In addition,the clinical manifestation of the 11 affected family members was found to be lateonset bilateral slowly progressive hearing loss,inherited in this family in an autosomal dominant manner.None of the affected family members had visual impairment or vestibular symptoms;therefore,we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.CONCLUSION We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants,and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.
文摘Hearing impairment is considered as the most prevalent impairment worldwide. Almost 600 million people in the world suffer from mild or moderate hearing impairment, an estimated 10% of the human population. Genetic factors play an important role in the pathogenesis of this disorder. Hereditary hearing loss is divided into syndromic hearing loss （associated with other anomalies） and non-syndromic hearing loss （not associated with other anomalies）. Approximately 80% of genetic deafness is non-syndromic. On the basis of the frequency of hearing loss, hereditary non-syndromic hearing loss can be divided into high-, mid-, low-, and total-frequency hearing loss. An audiometric finding of mid-frequency sensorineural hearing loss, or a ＂bowl-shaped＂ audiogram, is uncommon. Up to now, merely 7 loci have been linked to mid-frequency hearing loss. Only four genetic mid- frequency deafness genes, namely, DFNA10 （EYA4）, DFNA8/12 （TECTA）, DFNA13 （COLIIA2）, DFNA44 （CCDC50）, have been reported to date. This review summarizes the research progress of the four genes to draw attention to mid-frequency deafness genes.
文摘目的 研究一个家系中2例非综合征型遗传性聋患者的致病原因。方法 收集该耳聋家系临床检查结果资料,采集静脉血后提取DNA,应用全外显子组测序技术分析可疑致病基因,并通过Sanger测序对变异进行验证。结果 该家系中2代5人,先证者(Ⅱ-2,9岁)和其弟弟(Ⅱ-3)均为迟发性感音神经性听力损失,患者父母听力正常。先证者弟弟(Ⅱ-3)携带相同突变位点。基因检测结果显示,先证者携带CDH23基因c.4762C>T(p.ARG1588TRP)和c.6604G>A(p.ASP2202ASN)。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics, ACMG)遗传变异分类标准与指南分析显示,c.4762C>T和c.6604G>A位点均为致病突变。蛋白功能分析发现,变异后氨基酸改变造成蛋白结构发生改变,进而影响蛋白质功能。结论 CDH23基因c.4762C>T和c.6604G>A复合杂合突变位点组合很可能是该家系耳聋致病基因。
基金supported by grants from the National Basic Research Program of China(973 Program)(#2012CB967900),the Major State Basic Research Development Program of China (973 Program)(#2011CBA01000)the National Nature Science Foundation of China(NSFC#81400472)the National Natural Science Foundation of China(NSFC #81271082)
文摘In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.
文摘目的分析陕西省宝鸡地区新生儿常见遗传性耳聋基因突变情况,为遗传性耳聋患者的临床治疗提供参考依据。方法选取2021年1月至2023年4月在陕西宝鸡市妇幼保健院出生的1985例新生儿作为研究对象,采用微阵列芯片杂交法检测4种遗传性耳聋基因(GJB2、GJB3、SLC26A4和线粒体mt DNA 12S rRNA)15个位点,将耳聋基因检测结果进行统计分析。同时将陕西宝鸡地区新生儿耳聋基因突变情况与国内其他地区进行比较。结果1985例新生儿中检出耳聋基因突变108例(5.44%)其中GJB2携带率最高,为2.67%,SLC26A4携带率为2.02%,GJB3携带率为0.40%,线粒体mt DNA 12S rRNA携带率为0.35%;以GJB2(c.235 del C)突变率(1.86%)最高,其次为SLC26A4(c.IVS7-2 A>G)突变率(1.56%)。与国内其他地区比较,陕西宝鸡地区除线粒体mt DNA 12S rRNA(m.1555 A>G)突变率无差异外,GJB2(c.235 del C)、GJB3(c.538 C>T)、SLC26A4(c.IVS-27-2A>G)突变率均有差异。结论陕西宝鸡地区新生儿携带的耳聋基因突变以GJB2为主,该研究有助于及早查明该地区新生儿听力损失的病因,从而对遗传性耳聋患者进行早期干预。
文摘目的分析枣庄市4129例孕妇常见耳聋基因突变位点筛查结果,探讨枣庄市孕期女性常见耳聋基因突变分布特点及耳聋基因筛查的临床意义。方法选取2020年10月至2022年4月就诊于枣庄市妇幼保健院进行耳聋基因筛查的4129例孕妇为研究对象,经知情同意后采集外周血,利用高通量测序法检测18个耳聋相关基因共100个突变位点,分析各突变位点的检出率及分布情况。对耳聋基因携带者孕妇的配偶进行基因测序,并对孕妇妊娠结局进行随访。结果在4129例受检者中,共检出311例携带耳聋基因突变,总体突变携带率为7.53%。其中,GJB2突变携带者140例(3.39%),SLC26A4突变携带者105例(2.54%),GJB3突变携带者21例(0.51%),线粒体12S rRNA突变携带者34例(0.82%),TMC1突变携带者1例(0.02%),纯合或复合杂合突变者4例(0.10%),双基因突变携带者6例(0.15%)。线粒体12S rRNA基因突变者均未出现听力缺失,其新生儿也均通过了听力筛查。结论在枣庄市孕期女性常见耳聋基因突变位点中,阳性检出率较高的3种变异分别是GJB2235 del C(2.47%)、SLC26A4 IVS7-2 A>G(1.24%)和GJB2299 del AT(0.63%)。线粒体12S rRNA基因突变者均未出现听力缺失,与目前临床对氨基糖苷类药物的控制使用有关。针对产前孕妇进行耳聋基因热点变异筛查,明确本地区耳聋基因突变的人群特点,对有效实现遗传性耳聋的二级预防具有重要意义。
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.
