广西2016～2018年新生儿耳聋基因突变发生情况分析

［摘要］　目的　对广西2016-06～2018-12出生的6 590名新生儿的耳聋基因突变情况进行分析,为新生儿耳聋基因突变防控提供科学依据。方法　选择2016-06～2018-12在广西壮族自治区人民医院产科分娩的新生儿共6 590名取脐带血提取DNA,采用晶芯十五项遗传性耳聋基因突变检测试剂盒接受耳聋基因GJB2、SLC26A4、GJB3和线粒体DNA12SrRNA四个基因的突变位点筛查。结果　共检出耳聋基因突变携带者156名,突变总携带率为2.37%。突变发生率大小排列为GJB2>SLC26A4>线粒体DNA12SrRNA>GJB3,发生率分别占48.72%、34.62%、14.10%和2.56%。男女婴比较基因突变构成比差异无统计学意义（P>0.05）;不同年份基因突变构成比差异无统计学意义（P>0.05）。结论　广西2016～2018年间新生儿耳聋基因突变携带率与既往报道相近,未发现性别、年份基因突变构成比的差别。     

广西地区耳聋基因突变与人工耳蜗植入术后疗效的关联性研究

目的 探讨广西地区耳聋基因突变与人工耳蜗（CI）植入术后疗效的关联性,为评估CI术后疗效提供参考。方法 选择2012年7月至2019年12月在广西地区行CI植入术并行耳聋基因检测的广西语前聋患者104例,根据基因突变情况分为突变组（14例）和非突变组（90例）。应用听觉行为分级标准（CAP）和言语可懂评分标准（SIR）评分对患者术后3个月、6个月及12个月的疗效进行评估。结果 104例患者中有14例患者检出致聋基因突变,突变率为13.46%。GJB2基因突变2例,其中c.235delC纯合突变1例,c.299delC杂合突变1例。SLC26A4基因突变10例,其中c. IVS7-2A> G杂合突变8例,c. 919-2A> G/c. 1614+5G> A复合杂合突变2例。OTOF基因c.1273C> T/c.4994T> C复合杂合突变1例。TRIOBP基因c. 5185-2A> G/c. 3299C> A复合杂合1例。两组患者术后3个月、6个月和12个月的CAP、SIR评分均呈上升趋势（P<0.05）,但两组变化差异无统计学意义（P&g...     

中国人群MYO15A基因同义突变引起剪接异常导致的非综合征型耳聋分析

［摘要］　目的　对一个遗传性非综合征型耳聋家系的临床特征进行分析并鉴定其致聋基因突变,同时在大规模耳聋人群队列中对鉴定出的致病性突变致中国人群耳聋的特征进行分析。方法　完善家系成员的问卷调查、听力学检查、体格检査等临床检查,同时采集血液样本,通过耳聋相关基因的大规模平行测序(MPS)和生物信息学分析进行致病基因鉴定。总结及分析鉴定出的致病性突变在中国耳聋基因研究战略联盟(CDGC)耳聋数据库中的检出情况。结果　在一个早发性极重度感音神经性耳聋家系中鉴定出MYO15A基因NM_016239.4:c.8182C>G（p.Arg2728Gly）/c.9861C>T（p.Gly3287=）复合杂合突变,为该家系耳聋患者的致聋原因。其中MYO15A基因c.9861C>T（p.Gly3287=）同义突变通过改变剪接导致基因功能缺陷,其在中国广西壮族人群中次要等位基因频率为0.2%（3/1 438）,在其他人群及公共数据库中均未检出。结论　研究确定了MYO15A基因c.9861C>T（p.Gly3287=）在中国非综合征型耳聋患者中的致病性,该突变在中国广西壮族自治区富集明显。通过研究强调了在致病基因鉴定时,高频与同义突变并非过滤的绝对指标,尤其是在某些地区富集格外明显的突变,应格外注意。     

常见耳聋基因突变与区域及民族之间差异相关性研究进展

［摘要］　耳聋是人类主要的残疾病之一,严重影响患者的身心健康和生活质量。由遗传因素导致的耳聋占绝大多数,耳聋基因诊断已逐步发展为必要的筛查手段,不同国家、不同地区、不同种族及不同民族间常见耳聋基因GJB2、线粒体12S rRNA、SLC26A4和GJB3突变的频率及热点各有差异。该文针对常见耳聋基因突变与区域及民族之间差异相关性的研究进展进行综述。     

ESPN基因罕见纯合突变导致常染色体隐性遗传耳聋的基因诊断及人工耳蜗康复效果评价

［摘要］　目的　鉴定1例重度感音神经性耳聋患者的遗传病因,明确检出突变的致病性,以及患者人工耳蜗康复效果,为该家庭再生育提供遗传指导。方法　采集广西壮族自治区一个耳聋小家系样本3例,包括1例重度感音神经性耳聋患儿和其正常听力父母。对该家系成员进行病史调查、体格及听力学检查,采集外周静脉血。进行全基因组测序和生物信息学分析鉴定致病基因,评估人工耳蜗术后听觉与言语康复效果。结果　ESPN基因c.1916-1G>A纯合突变是该家系的致聋原因,人工耳蜗术后听觉与言语康复效果良好。结论　研究发现了ESPN基因一个新的突变,是该耳聋家系的致病原因。回访发现人工耳蜗术后患儿言语康复效果好。该研究丰富了遗传性聋的突变谱,并对人工耳蜗植入的术前评估具有指导意义。     

遗传性家族性头颈副神经节瘤三个家系的SDH基因家族变异分析

［摘要］　目的　对三个遗传性家族性头颈副神经节瘤家系进行SDH基因家族变异分析。方法　选择2022年1月至2023年12月四川大学华西医院耳鼻咽喉头颈外科收治的3例头颈副神经节瘤患者（先证者）及其家系成员,采集研究对象外周静脉血200 μL,提取基因组DNA后进行测序,并对候选变异进行Sanger测序和致病性分析。结果　三个家系分别诊断为SDHD NM_003002.4:c.1A>G、SDHD NM_003002.4:c.274G>T和SDHB NM_003000.3:c.689G>A杂合变异导致的副神经节瘤,均为已报道过的变异。结论　对头颈副神经节瘤患者开展基因检测可以明确其致病原因,为遗传咨询提供参考。     

镫骨强直伴拇指（趾）宽大综合征家系NOG基因新发突变鉴定及临床特征分析

［摘要］　目的　分析一个罕见的镫骨强直伴拇指（趾）宽大综合征(SABTT)家系（编号HuB-341）的临床及遗传学特征,应用新一代高通量测序鉴定其致病基因。方法　对该家系成员进行病史调查、体格检查、影像学检查以及听力学检查,绘制家系图谱。同时抽取家系成员外周静脉血并提取DNA,对先证者进行全外显子组测序,对候选基因通过Sanger测序进行家系验证,明确该家系的致病基因。结果　HuB-341家系来自湖北省武汉市,2代3人。先证者为家系唯一耳聋患者,临床表现为双耳传导性聋并伴有特征性面容、拇趾宽大、弱视及远视。对先证者进行全外显子组测序鉴定了NOG基因一个新的突变位点,即c.679G>T,引起编码第227位的谷氨酸突变为终止密码子（p.Glu227Ter）。家系验证提示该突变为新生突变。该突变在多物种间是保守的。结论　该家系临床诊断为SABTT,通过先证者全外显子组测序及家系验证,鉴定了NOG基因一个新的突变位点,即c.679G>T（p.Glu227Ter）。该突变为家系的致病突变,临床诊断和分子诊断相结合提高了对该罕见病的认识,为该家系的遗传咨询提供了科学依据。     

SCN8A基因突变相关癫痫患儿8例的临床与遗传学特征分析

［摘要］　目的　分析SCN8A基因突变相关癫痫脑病的临床与遗传学特征。方法　选择2018年1月至2020年12月福建省立医院儿科收治的SCN8A基因突变相关癫痫病患儿8例，均经医学外显子测序及Sanger测序验证。收集其临床病历资料和基因检测结果进行总结分析。结果　8例患儿起病年龄中位数为6个月，男6例，女2例。癫痫发作类型有7种，3例存在≥3种发作类型。出现言语迟缓5例，肌张力低下4例，共济失调4例，步态障碍2例，智力低下5例。除1例脑电图正常外，其余7例发作间期脑电图异常，主要为多灶性放电。8例均为错义突变，其中未报道突变4例。新发突变5例，遗传杂合突变3例，临床表型各有差异。3例位于结构域C端内的突变，表型也有差异。结论　SCN8A基因相关癫痫是一种谱系疾病，新发突变可出现轻度温和至重度癫痫脑病表现，遗传杂合突变也可出现癫痫脑病的表现。突变方式与表型无相关性。突变位点在结构域中分布与突变来源及临床表型无关联。     

右美托咪定联合氯胺酮用于小儿眼科手术的临床观察

［摘要］　目的　观察右美托咪定联合氯胺酮用于小儿眼科手术的安全性及麻醉效果。方法　选择90例2～7岁行眼科手术的患儿,随机分为三组,每组30例。A组使用氯胺酮联合右美托咪定麻醉,B组使用氯胺酮联合咪唑安定麻醉,C组单纯使用氯胺酮麻醉。记录麻醉前（T0）、肌注氯胺酮后5 min(T1)、手术开始时(T2)、手术开始后5 min(T3)、手术开始后15 min(T4)及手术结束时(T5)的收缩压（SBP）、舒张压（DBP）、心率（HR）、血氧饱和度（SpO₂）,并记录三组患儿氯胺酮总用量及术中不良反应,观察术后苏醒时间、苏醒期躁动发生情况。结果　A组与C组比较,T1、T3、T5的SBP和T5的DBP差异有统计学意义（P<0.05）。A组HR在T5时点与B、C两组比较差异有统计学意义（P<0.05）。A、B两组氯胺酮总用量和术中不良反应发生例数与C组比较差异有统计学意义（P<0.05）。A、B两组苏醒时间、苏醒期躁动发生例数均少于C组,而A组明显优于B组（P<0.05）。结论　右美托咪定联合氯胺酮用于小儿眼科手术麻醉是安全的,且术中血流动力学平稳,不良反应少,术后苏醒时间短,苏醒期躁动发生例数减少。     

ABCB1基因多态性对慢性粒细胞白血病及胃肠道间质瘤患者治疗药物伊马替尼血药浓度影响的Meta分析

［摘要］　目的　系统性评价ABCB1基因多态性对慢性粒细胞白血病及胃肠道间质瘤患者治疗药物伊马替尼血药浓度水平的影响,为临床个体化用药提供循证依据。方法　检索PubMed、EMBASE、Web of Sciences、Scopus、中国知网和万方数据库,搜集伊马替尼药动学通路转运体的ABCB1 C1236T、G2677T/A、C3435T基因多态性与接受伊马替尼治疗患者血药浓度的相关性研究。按照纳入及排除标准进行文献筛选、数据提取工作,并进行Meta分析。结果　共纳入ABCB1基因多态性与伊马替尼血药浓度水平相关性研究7篇,合计873例患者。Meta分析结果显示,ABCB1 C1236T中T等位基因携带者与C等位基因携带者间伊马替尼的稳态血药浓度差异有统计学意义（WMD=97.44 ng/ml,P=0.03）,G2677T/A中突变纯合及杂合基因携带者与野生型基因携带者间伊马替尼血药浓度差异有统计学意义（WMD=318.27 ng/ml,P<0.01）,未显示C3435T基因多态性与伊马替尼血药浓度具有显著关联性（P>0.05）。结论　ABCB1 C1236T、G2677T/A突变基因与伊马替尼血液浓度升高有关。     

Advances in hereditary deafness

Progress in the Human Genome Project, availability of cochlea-specific cDNA libraries, and development of murine models of deafness have resulted in rapid discovery of many loci and corresponding genes for deafness. Up to now, the chromosomal locations of about 70 genes for non-syndromic deafness have been mapped, and the genes of more than 20 loci have been identified and characterised. Mutations in one gene, connexin 26 (CX26GJB2), are responsible for most cases of recessive non-syndromic deafness, accounting for 30-40% of all childhood genetic deafness in some populations (eg, white people of western European descent). We summarise advances in identification of genes for deafness and provide a guide to the clinical approach to diagnosis of patients with hearing loss.     

Idiopathic sudden deafness

PURPOSE: Sudden idiopathic deafness is a sensorineural hearing loss with no recognized causes at the time of onset. The impairment site is usually localized in the cochlea, but some cases of retrocochlear lesions (e.g., cerebellopontine angle tumors, degenerative neural diseases, neuraxial ischemic lesions) can induce sensorineural deafness. The medical management of patients presenting with sudden deafness aims at detecting a causal mechanism, and at administering emergency therapeutic drugs. The diagnosis of idiopathic sudden deafness can be definitely made when no causes are found. Usually, the impairing mechanism involves the cochlea. The pathophysiology of this sensorineural alteration is still unknown. It is most likely that several mechanisms are associated together, their common point being an impairment to the feedback loop of the organ of Corti. CURRENT KNOWLEDGE AND KEY POINTS: It is very likely that reactivation of neurotropic viruses and/or cochlear ischemia are frequent etiologies. Whatever the cause, the treatment is to be administered urgently, and consists of a high-dose corticotherapy at the least. Other treatments have never really proven to be effective. It is secondarily checked that no retrocochlear pathological processes, such as a cerebellopontine angle tumor, is present, in particular in young people. FUTURE PROSPECTS AND PROJECTS: One of the current objectives is to determine when cochlear ischemia is involved, in a mini-invasive manner, such as with laser Doppler flowmetry, so that the treatment can be optimized. From a therapeutic point of view, early acoustic protection has been proven to be effective in cases of cochlear ischemia in small laboratory animals. Its efficacy in case of sudden deafness, non-exclusive of other causes than ischemia, is being assessed in a multicentric project.     

Syntax-induced pattern deafness

Perceptual systems often force systematically biased interpretations upon sensory input. These interpretations are obligatory, inaccessible to conscious control, and prevent observers from perceiving alternative percepts. Here we report a similarly impenetrable phenomenon in the domain of language, where the syntactic system prevents listeners from detecting a simple perceptual pattern. Healthy human adults listened to three-word sequences conforming to patterns readily learned even by honeybees, rats, and sleeping human neonates. Specifically, sequences either started or ended with two words from the same syntactic category (e.g., noun–noun–verb or verb–verb–noun). Although participants readily processed the categories and learned repetition patterns over nonsyntactic categories (e.g., animal–animal–clothes), they failed to learn the repetition pattern over syntactic categories, even when explicitly instructed to look for it. Further experiments revealed that participants successfully learned the repetition patterns only when they were consistent with syntactically possible structures, irrespective of whether these structures were attested in English or in other languages unknown to the participants. When the repetition patterns did not match such syntactically possible structures, participants failed to learn them. Our results suggest that when human adults hear a string of nouns and verbs, their syntactic system obligatorily attempts an interpretation (e.g., in terms of subjects, objects, and predicates). As a result, subjects fail to perceive the simpler pattern of repetitions—a form of syntax-induced pattern deafness that is reminiscent of how other perceptual systems force specific interpretations upon sensory input.     

Inner ear deafness in Wegener's granulomatosis.

Autoimmune deafness represents a heterogeneous group of disorders in which there is though to be inner ear and/or middle ear damage mediated by various immunological abnormalities. We describe a patient with Wegener's granulomatosis in whom there was evidence of significant inner ear damage caused by vasculitis, which was completely reversed by cyclophosphamide and prednisolone. We propose that Wegener's granulomatosis is a cause of autoimmune deafness.