广东地区非综合征型耳聋突变基因流行病学调查

目的揭示广东地区非综合征型耳聋(Non-syndromic hearing loss,NSHL)患者的分子病因构成,为规范标准的聋病筛查、预防及干预提供理论依据。方法对广东地区507例NSHL患者抽取外周静脉全血并提取基因组DNA,检测中国人群中常见的4个耳聋基因9个突变位点。结果 507例NSHL患者共检出耳聋基因突变者115例(115/507,22.68%)。其中GJB2基因突变携带者48例,检出率9.47%(48/507):包含c.235 del C纯合突变型6.31%(32/507),杂合突变型1.58%(8/507);c.299 del AT纯合突变型0.20%(1/507),杂合突变型0.40%(2/507);c.235 del C/c.299 del AT复合杂合突变型0.99%(5/507)。SLC26A4基因59例,检出率11.64%(59/507):包含c.919-2 A>G纯合突变型3.16%(16/507),杂合突变型6.11%(31/507);c.2168 A>G纯合突变型0.40%(2/507),杂合突变型1.38%(7/507);c.919-2 A>G/c.2168 A>G复合杂合突变型0.59%(3/507)。线粒体12S r RNA检出8例(8/507,1.58%),均为m.1555 A>G均质型突变。结论 SLC26A4是广东地区NSHL人群最主要的致聋基因,c.919-2A>G为其突变热点;GJB2为引起该地区SNHL的第二位致聋基因,c.235del C为其突变热点。     

连接蛋白与遗传性耳聋

耳聋的遗传基础比较复杂，具有很强的遗传异质性。在人类约有15种连接蛋白，现证实有4种连接蛋白与遗传性耳聋有关，本从它们在组织和器官的表达、突变类型、引起耳聋的机制及临床应用等方面的研究进展进行综述。     

南通地区遗传性耳聋资源收集及病因学分析

目的 调查江苏南通地区遗传性耳聋病因流行病学情况。方法 调查南通各市县五个聋哑学校202名学生，利用聚合酶链反应一限制性片断长度多态性（PCR—RFLP）方法和Prev—DAF药物性耳聋基因诊断试剂盒筛查患者GJB2 235delC突变和线粒体DNA 12SrRNA A1555G突变。结果 195例非综合征耳聋患儿中31例（15．9％）为GJB2 235delC纯合突变，21例（10.8％）为GJB2 235delC杂合突变，5例（2．6％）存在线粒体DNA 12SrRNA A1555G点突变，在分子水平能够明确诊断者占2913％。结论 南通地区遗传性耳聋发病率较高，尤其是GJB2 235delC突变，突变率（26％）明显高于全国平均水平（18％）。此结果突出了本地区耳聋基因诊断的重要作用，利用耳聋基因检测技术，在人群中（包括重点人群和普通人群）进行生育前耳聋基因筛查，是达到减少聋儿出生的重要途径。     

遗传性耳聋与肌球蛋白

肌球蛋白家族在遗传性耳聋的致病机理中具有重要作用。本详述了近年来发现的与遗传性耳聋表型特征相关的肌球蛋白基因的作用及功能，对理解遗传性耳聋的分子病理机制提供帮助。     

X-连锁遗传性耳聋的研究进展

耳聋是一种常见的公共健康问题,对社会经济造成极大的损失。X染色体基因突变可引起综合征型遗传性耳聋和非综合征型耳聋,其中非综合征型耳聋相关位点报道甚少。本文针对引起非综合征型耳聋和部分综合征型耳聋的X连锁耳聋基因与位点进行综述,并探讨X连锁耳聋家系的研究策略。     

中国人群遗传性耳聋研究进展

耳聋有着复杂的病因学特点，遗传和／或环境因素均可致聋。120多个耳聋相关基因的发现为我们了解听觉的病理生理机制提供了新的视点。然而，最近的研究表明在中国相当一部分综合征性和非综合征性耳聋仅由为数不多的几个基因突变引起。本文旨在综述综合征性、非综合征性及线粒体遗传性聋在中国人群感音神经性聋致病机制方面的最新进展。深入了解中国人群耳聋分子病因学特点，对获得准确的耳聋早期诊断和遗传咨询，以便及时干预和治疗至关重要。     

烟台地区3785例新生儿遗传性耳聋基因位点筛查分析

目的 评估烟台地区新生儿耳聋基因的突变情况,为遗传性耳聋患者的临床治疗提供参考。方法 采集3785例出生3d的新生儿足底血血斑,提取人基因组DNA。利用微阵列芯片杂交法检测4个遗传性耳聋基因(GJB2、GJB3、SLC26A4及mtDNA 12S rRNA)15个位点,并用Sanger测序法对突变位点进行确证。将烟台地区新生儿耳聋基因突变情况与山东省平均突变情况进行比较。同时,针对相同的检测方法(微阵列芯片检测法)和相同的筛查位点(4个基因15个位点),将烟台地区与淄博地区进行耳聋基因突变情况的比较。结果 3785例新生儿共检出255例耳聋基因突变携带者,突变率为6.74%(255/3785)。单基因突变242例,包括134例GJB2、85例SLC26A4、12例GJB3和11例mt DNA 12S rRNA,其突变率分别是3.55%、2.25%、0.32%和0.29%。两个位点复合突变13例,其中非等位基因复合突变6例,等位基因复合突变5例,2例核基因与线粒体基因复合突变。烟台地区耳聋基因总突变率和GJB2基因突变率明显高于山东省平均突变情况(χ²=32.20,...     

新生儿遗传性耳聋及听力筛查

耳聋是人类一种最常见的感觉系统缺陷。在世界范围内新生儿中听力障碍率为0.1～0.3%,其中约50%系遗传因素所致。遗传性听力损失根据是否伴有耳外组织的异常或病变分为综合症性听力损失     

DFNA5与遗传性耳聋

遗传性耳聋是危害人类健康的重大疾病之一,根据是否合并其他系统器官疾病,分为综合征性耳聋和非综合征性耳聋,而非综合征性耳聋具有很高的遗传异质性.迄今为止,常染色体显性遗传非综合征性耳聋(DFNA)已成功定位了64个位点,24个基因(Hereditary Hearing Loss Homepage:http://webhost.ua.ac.be/hhh/).第五个常染色体显性遗传非综合征性耳聋基因DFNA 5(OMIM 600994)于1995年在一个高频进展性听力下降的荷兰家系中首先定位在7p15[1],1998年确认了DFNA5的致聋基因[2].本文就已报道DFNA5的基因突变特点、家系的临床特征及目前对该基因功能的研究进展等方面进行综述.     

湖南地区4132例备孕女性遗传性耳聋基因筛查结果分析

目的 探讨湖南地区4132例备孕女性遗传性耳聋基因筛查结果特点.方法 通过多重PCR扩增、高通量测序等技术联合,对18个耳聋致病基因的108个突变位点进行筛查,对阳性样本中的突变基因、位点以及突变阳性率等特点进行统计分析.结果 4132例检测样本中,阳性202例,检出率为4.89％.单基因突变型200例,包括SLC26...     

Epidemiological survey of acute low-tone sensorineural hearing loss

Abstract

Objectives: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically.

Methods: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student’s t-test, χ² test and logistic regression.

Results: Female gender (p?<?.013), younger age (p?<?.001), low-grade hearing loss (p?<?.001), and shorter interval between onset and initial visit (p?<?.004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p?<?.007).

Conclusions: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.     

An overview of hereditary hearing loss

Understanding the genetic basis of hearing loss is important because almost 50% of profound hearing loss are caused by genetic factors and more than 120 independent genes have been identified. In this review, after a brief explanation of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype and phenotype), classification of genetic hearing loss (syndromic versus nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed. Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen, Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes, biotinidase deficiency and Norrie disease) causing genetic hearing loss were also explained briefly. The genes involved in hearing loss and genetic heterogeneity were presented.     

PRPS1基因突变与遗传性耳聋

磷酸核糖焦磷酸合成酶（phosphoribosylpy-rophosphate synthetase,简称PRS,EC2.7.6.1）,又称核糖磷酸焦磷酸激酶（Ribose-phosphate pyrophos-phokinase）,是体内唯一的催化磷酸核糖焦磷酸（PRPP）合成的酶,而PRPP是体内嘌呤、     

Functional study of GJB2 in hereditary hearing loss

OBJECTIVES/HYPOTHESIS: The gene of the gap junction protein connexin 26 (Cx26) was found to be the main causative gene of autosomal recessive nonsyndromic hearing loss (DFNB1). Although 35delG has been known as the major mutation in Western countries, 235delC was reported to be a specific form of mutation in Asian populations. The objective of the study was to identify how 235delC and E114G changes found in the Korean population affected the function of using molecular biological techniques. METHODS: Genes containing 235delC and E114G were cloned into the pcDNA3 vector, and HeLa cells were transfected with the recombinant DNA samples by the liposome complex method. The expression and subcellular localization of Cx26 were determined, using antibodies against amino acid sequences in the intracellular loop (IL) and N-terminal (NT) portions of Cx26. To analyze functions of the as a gap junction channel, we examined Lucifer yellow dye transfer between cells with a scrape-loaded technique. Wild-type (WT) with normal hearing was used as a positive control, and mock transfected cells were used as a negative control. RESULTS: Immunocytochemical analysis showed that cells transfected with E114G and WT gave characteristic punctate patterns of reaction in the cell membrane with both antibodies. However, 235delC cells were not stained with anti-IL antibody but stained slightly just around the nucleus only with anti-NT antibody. In a functional study of, transfer of Lucifer yellow into contiguous cells was detected in both WT and E114G, but no transfer activity was observed in 235delC. CONCLUSIONS: The 235delC mutation showed a loss of targeting activity to the cell membrane and severe deterioration of gap junction activity. For the E114G, we did not find any difference from WT transfected cells.     

Noncongenital hereditary hearing loss in children. Prospective documentation

Younger siblings of children with sensorineural hearing loss of possible hereditary cause underwent interval audiologic examination. Seven siblings (in unrelated families) were found to have progressive sensorineural hearing loss despite early audiograms documenting normal hearing levels for age. Continued testing of these children allowed for early identification and intervention. We advocate regular otolaryngologic and audiologic follow-up even after normal audiologic assessments are made for younger siblings of children with documented sensorineural hearing loss, unless a definite nongenetic origin of the hearing loss in the older child is known. Recessive sensorineural hearing loss with onset in infancy or childhood may present with no antecedent family history and with normal behavioral audiograms early in life.     

MYO7A基因突变与遗传性耳聋

耳聋是临床上最常见的遗传性疾病之一。在所有耳聋患者中,遗传性聋约占50%,在所有先天性聋儿中,60%以上由遗传因素引起。与遗传性耳聋相关的基因大约有200多个,     

缝隙连接蛋白31基因与遗传性耳聋

遗传性耳聋作为-种单基因疾病,具有明显的遗传异质性,迄今共有187个耳聋位点（54个为常染色体显性位点,67个为常染色体隐性位点,8个X-连锁位点,2个修饰基因位点,1个Y-连锁位点,1个听神经病基因位点,13个线粒体DNA突变位点．8个与耳硬化症有关的基因位点．33个与综合征性耳聋有关的位点）见诸报道,已克隆的听觉基因共73个,其中45个与非综合征性耳聋有关。研究表明,耳聋与多种缝隙连接蛋白（Connexin,CX）突变有关．缝隙连接对于维持正常听觉功能有着重要的作用。人耳可听到的声音频率在20～20000Hz之间．并可感受到相差100万倍以上的声强变化。听觉器官的灵敏度与频率选择性分别为听力阈值与语言识别能力的基础。     

耳聋遗传学病因分析

目的 对耳聋患儿进行GJB2、线粒体DNA1555位点及PDS基因突变检测,为遗传性耳聋提供诊断依据.方法 收集门诊68例散发非综合征型耳聋患儿及80例健康对照个体的外周血DNA样本共148份;采用聚合酶链反应(polymerase chain reaction,PCR)分析方法扩增GJB2(gap junction beta2)、线粒体DNA A1555G(mitochondria DNA A1555G,mtDNAA1555G)及SLC26A4基因片断,行限制性酶切分析和序列分析.结果 病患组发现GJB2基因235delC纯合突变、235delC与176-191del16复合及235delC与299-300delAT复合突变等共13例耳聋患儿与GJB2基因突变有关,占19.12%.病患组235delC等位基因频率为14.71%,正常对照组为1.25%(P＜0.01).同时在病患组还发现了线粒体DNA A1555G突变及大前庭水管综合征SLC26A4(IVS7-2A＞G)纯合突变.结论 深入研究及分析各耳聋相关基因所致疾病的不同表型,选择适当的临床基因检测方法,为耳聋患者提供经济、有效的基因诊断.