遗传性耳聋家系线粒体DNA 961delT/insC(n)突变的致病性分析

目的 探讨线粒体DNA 961delT/insC(n)突变与氨基甙类药物性耳聋的相关性.方法 对一个耳聋家系11个成员采集氨基甙类抗生素用药史、进行听力学检查、表型分析,采集外周静脉血样本,从白细胞中提取DNA,用聚合酶链反应扩增线粒体DNA(mtDNA)全序列,对扩增片段进行DNA测序,对发现的基因突变与耳聋表型进行分离分析.结果 参与研究的所有9例母系成员均检出mtDNA 961delT/insC(n)突变.有明确氨基甙类抗生素用药史的4例中只有2例耳聋患者,其中1例为用药之前出现的先天性聋,另1例为用药后38年出现的轻度耳聋.突变不与耳聋共分离.结论 本研究不支持mtDNA 961de1T/insC(n)突变是该家系耳聋的致病突变,mtDNA 961位点附近可能是一个多变异的区域,mtDNA 961delT/insC(n)可能是一个与氨基甙类药物性耳聋不明确相关的多态.     

Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA

The A1555G mutation in the mitochondrial 12S ribosomal RNA gene is often found in patients with hearing loss after aminoglycoside exposure. A second pathogenic mutation in this gene, deletion of thymidine at position 961 with varying numbers of cytosines inserted (delT961Cn), has recently been found to predispose patients to aminoglycoside-induced deafness. We report on a Japanese patient bearing the delT961Cn who had streptomycin-induced deafness. Our report suggests that the delT961Cn plays an important secondary role in the pathogenesis of deafness caused by aminoglycosides. The combination of taking family histories and molecular screening at the 1555 and 961 positions is thought to reduce the frequency of tragic irreversible deafness due to aminoglycosides.     

The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population

Several mitochondrial DNA variants increase risk for developing sensorineural hearing loss following exposure to aminoglycoside antibiotics, a particular concern in the premature infant population, as many of these babies spend time in neonatal intensive care units and are treated with aminoglycosides. To determine the relative prevalence of five mitochondrial DNA variants in the 12S rRNA gene, MT-RNR1, we genotyped 703 neonatal intensive care unit patients and 1473 individuals from the general Iowa population. We found that the aggregate frequency of these variants (～1.8%) was comparable between populations. Although no hearing loss was detected by newborn hearing screens in the at-risk patients, these neonatal intensive care unit graduates have an increased life-time risk for developing aminoglycoside-induced deafness.     

感音神经性听力损失的MRI特征

感音神经性听力损失(SNHL)是耳科常见疾病,主要表现为听力损失伴或不伴耳鸣、眩晕、耳闷等症状,SNHL病因复杂多样,目前尚未有一个确切的病因。近年来磁共振影像技术(MRI)得到了较好的发展和运用,内听道MRI在显示软组织方面更具优势,可用来研究SNHL患者的内耳疾病,如研究小脑前下动脉来进一步阐述内耳微循环,轧造影显示梅尼埃病患者膜迷路积水,以及功能MRI对脑区活动的研究等等。本文主要以内听道MRI影像学特征来探讨SNHL的潜在病因,为耳科医生诊疗SNHL提供新思路。     

Hereditary sensorineural hearing loss of unknown cause involving mitochondrial DNA 1555 mutation

We report on a family with maternally inherited sensorineural hearing loss, in which no history of aminoglycoside injection and no other specific etiology could be identified in any member. A 1555 A-to-G mutation of mitochondrial DNA was found in all members demonstrating hearing loss. The hearing in the propositus and his sister was severely impaired at a younger age than that in the mother. This case suggests that the 1555 point mutation of mitochondrial DNA has potential to promote inherited nonsyndromic hearing loss without any known etiology.     

急性双耳感音神经性聋19例病因及临床特点分析

目的 探讨急性双耳感音神经性聋的病因及其相应的临床特点,为临床诊疗提供借鉴.方法 回顾性分析2000年11月至2013年12月期间共19例以急性双耳感音神经性聋为主要首发症状患者的临床资料,分别对其临床特征、全身系统检查、实验室检查、听力学及影像学特征进行整理分析,归纳病因,并追踪临床诊疗及预后.结果 19例患者中非耳科系统疾病15例,占78.9％.大部分病例呈现多系统、多器官受累:3例为中枢神经系统疾病,包括真菌性脑膜炎、结核性脑膜炎以及病毒性脑炎各1例,耳聋为双侧进行性加重,伴有发热、头痛、头晕,恶心、呕吐及精神状态的改变等,言语识别率下降,言语识别阈不成比例地明显差于纯音听阈;5例为免疫系统疾病,包括抗中性粒细胞胞质抗体相关小血管炎、复发性多软骨炎、类风湿性关节炎和系统性红斑狼疮,耳聋累及双侧、进展快,同时存在自身免疫性疾病的特点;5例为血液内分泌系统疾病,包括糖尿病、白血病和甲状腺功能低下,听力下降多为双侧对称性、进展性;4例为耳科系统疾病,包括大前庭水管综合征和突发性聋;另有2例为药物性聋.在经过针对病因治疗后,19例患者中,痊愈1例,显效3例,有效7例,无效(亦包括死亡及放弃治疗的病例)8例,总有效率为57.9％.结论 急性双耳感音神经性聋多与全身系统性疾病相关,临床诊治上应详细分析病史、临床表现,并完善实验室检查、听力学及影像学等检查以明确诊断,针对病因积极治疗.     

母系遗传性聋大家系听力学调查及线粒体DNA突变分析

目的　探讨母系遗传性非综合征性耳聋的听力学特征及分子遗传学机制。方法　选择一遗传聋大家系中 4代 41人为研究对象 ,详细询问病史和全身体格检查 ,行系统听力学测试和线粒体DNA(mtDNA)A15 5 5G突变分析。结果　 2 0例母系亲属均存在A15 5 5G点突变 ;纯音测听 17例呈程度不等的感音神经性聋 ,双耳对称 ,发病年龄 1～ 5 0岁 ,5例听力近 11年间呈进行性下降 ;声导抗测试均为A型鼓室曲线 ,12耳可在低感觉级引出镫骨肌反射 ;听性脑干反应 (auditorybrainstemresponse,ABR)和瞬态诱发耳声发射测试无蜗后病变证据。 2 1名父系亲属及配偶无听力障碍 ,mtDNAA15 5 5G突变检测阴性。结论　本家系以迟发性进行性耳蜗性聋为特点 ,导致听力损失的内在因素为mtDNAA15 5 5G突变 ,而环境因素和核基因可能也参与了突变体mtDNA表型表达的调节。     

Progressive sensorineural hearing loss in children with mitochondrial encephalomyopathies

OBJECTIVE: Mitochondrial disorders are responsible for a variety of neurological syndromes. Specific mitochondrial DNA mutations have been identified recently in some of these rare disorders. Clinical symptoms may occur in different organs to various extent; often they are associated with progressive hearing loss. The aims of this study were to determine incidence, onset, and characteristics of hearing loss in children with mitochondrial encephalomyopathies and to investigate a possible correlation between the degree of hearing loss and neurological symptoms. In addition, we investigated the prognostic value of hearing loss as a predictor of the disease. STUDY DESIGN: From August 1992 to September 1998, 29 patients ranging in age from 5 to 23 years (mean years) were studied. These children were hospitalized for diagnostic purposes in the neuropediatric department. METHODS: The mitochondrial disorder was diagnosed by clinical and laboratory testings, including analysis of the mtDNA. Audiological evaluation consisted of measurements of pure-tone and speech audiometry, tympanometry, and acoustic refle- threshold testing, auditory brainstem response, and evoked as well as distortion-product otoacoustic emissions. RESULTS: A sensorineural hearing loss was identified in 12 children. Three of these were diagnosed as having classic Kearns-Sayre syndrome; five as having multisystem KSS; two as having the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); one as having KSS-MELAS overlap syndrome; and one as having Friedreich ataxia. Longitudinal testing was performed in seven children, and in all of them a progression of the hearing loss could be demonstrated. Audiological test results in all 12 children suggested cochlear as well as retrocochlear origin of the hearing loss presenting independently from the severity of hearing impairment. No correlation between the characteristics and degrees of hearing loss and the number and severity of clinical neurological symptoms could be found. CONCLUSIONS: The present study demonstrated a high incidence (42%) of sensorineural hearing loss in children with mitochondrial encephalomyopathies. The progressive nature of the hearing impairment was confirmed by a significant correlation between the duration in years and severity of hearing loss in the children. The hearing loss does not have a prognostic value for the progression of the disorder. Based on our findings, we recommend regular audiometric examinations in patients with mitochondrial disorders.     

Bilateral sensorineural hearing loss in members of a maternal lineage with a mitochondrial point mutation

Pure-tone audiometry was carried out on members of a recently described maternal lineage with sensorineural deafness, harbouring a novel mitochondrial mutation in the gene for tRNA-ser(UCN). This revealed a characteristic pattern of symmetrical bilateral sensorineural hearing losses in each affected individual, predominantly affecting the high-frequencies, but with considerable variability between individuals. No clear correlation was observed between age and severity, but most subjects reported progressive worsening of their condition. Some members of the lineage were found to be heteroplasmic for the tRNA-ser(UCN) mutation. However, the severity of hearing loss was poorly correlated with the representation of the mutant mtDNA, indicating that other, as yet unidentified factors must be involved in the aetiology of this disorder.     

Acute sensorineural hearing loss associated with aortitis syndrome

CONCLUSIONS: Steroid treatment was effective in improving hearing in most episodes in our and previously reported patients with acute hearing loss associated with aortitis syndrome. This suggests that inflammatory changes due to autoimmune responses may play an important role in the manifestation of hearing loss in aortitis syndrome. OBJECTIVES: To clarify clinical features in patients with aortitis syndrome who exhibited hearing loss. CASE REPORTS: We describe two patients, 39-year-old and 53-year old women, who developed several episodes of acute sensorineural hearing loss associated with aortitis syndrome. RESULTS: In both patients, hearing loss involved the cochlea and hearing recovered following corticosteroid treatment. A literature review revealed that hearing loss was commonly manifested in middle-aged females and involved bilateral ears. Corticosteroid treatment was effective in improving hearing in most episodes in the previously reported cases as in our patients.     

Angiostrongylus eosinophilic meningitis associated with sensorineural hearing loss

A 59-year-old woman who presented with chronic headache, neck stiffness and left-sided hearing loss is reported. The diagnosis of angiostrongylus eosinophilic menigitis was made. The patient improved after treatment with prednisolone, including hearing. Angiostrongylus eosinophilic meningitis associated with sensorineural hearing loss has not previously been reported.     

Steroid-responsive sensorineural hearing loss associated with aortitis syndrome

Five cases of sensorineural hearing loss associated with aortitis syndrome are presented, and their clinical features are discussed in detail. All patients were middle-aged females. Pure-tone audiometry revealed a high-tone gradual-loss type of configuration, and the recruitment phenomenon was proved to be positive in most cases. The degree of hearing loss correlated well with the erythrocyte sedimentation rate. However, the most remarkable clinical feature was that the hearing loss showed steroid responsiveness in all cases. Based on these clinical features, it was suggested that the steroid-responsive sensorineural hearing loss associated with this syndrome might not be an incidental accompanying symptom but rather one of the local manifestations of the disease arising from similar mechanisms as the systemic inflammatory process. Associated conductive disturbance is also discussed.     

母系遗传性聋大家系听力学调查及线粒体DNA突变分析

目的 探讨母系遗传性非综合征性耳聋的听力学特征及分子遗传学机制。方法 选择一遗传聋大家系中４代４１人为研究对象,详细询问病史和全身体格检查,行系统听力学测试和线粒体ＤＮＡ（ｍｔＤＮＡ）Ａｌ５５５Ｇ突变分析。结果 ２０例母亲亲属均存在Ａ１５５５Ｇ点突变,纯音测听１７例呈程度不等的感音神经性聋,双耳对称,发病年龄１～５０－岁,５例听力近１１年间呈进行性下降,声导抗测试均为Ａ型鼓室曲线,１２耳可在低感觉     

Isolated hearing loss associated with T7511C mutation in mitochondrial DNA

CONCLUSION: The T7511C mutation is considered responsible for maternally inherited, isolated sensorineural hearing loss of cochlear origin. This mutation should be screened for in cases of nonsyndromic, familial sensorineural hearing loss compatible with maternal transmission. OBJECTIVES: To clarify the audiovestibular phenotype characteristics associated with a T7511C mutation in mitochondrial DNA and determine whether it causes isolated sensorineural hearing loss unaccompanied by other neuromuscular symptoms or signs. SUBJECTS AND METHODS: A proband and affected members of a Japanese family harboring a T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene were enrolled. Mutation analysis was done on genomic DNA extracted from blood samples. Auditory pathways involved were investigated in examinations that included pure-tone audiograms, acoustic reflexes, speech discrimination testing, distortion-product otoacoustic emissions, and auditory brainstem responses. The presence of other signs and symptoms, including vestibular ones, was investigated. RESULTS: We identified a homoplasmic T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene in this family. No other pathogenic mutations associated with hearing loss or common mitochondrial diseases were found. Hearing loss of cochlear origin mainly developed at mid to high frequencies. Vestibular systems were well preserved. No symptoms or signs characteristic of mitochondrial diseases were present in any family members.     

Chiari-I malformation associated with asymmetric sensorineural hearing loss.

Chiari-I malformation is a deformity of the structures of the posterior fossa in which there is inferior herniation of the cerebellar tonsils through the foramen magnum without significant caudal dislocation of the brainstem. Patients are usually asymptomatic until adulthood, when they commonly present with recurrent headaches, weakness, vertigo and/or imbalance, nystagmus and hearing loss. A review of 226 consecutive patients evaluated for asymmetric sensorineural hearing loss revealed 32 patients with retrocochlear pathology. Three of these patients were discovered to have a Chiari-I malformation by magnetic resonance imaging as their only pathology. We suggest a possible association between a Chiari-I malformation and isolated asymmetric sensorineural hearing loss secondary to long-standing traction on the eighth cranial nerve.     

Bilateral sensorineural hearing loss associated with Mycoplasma pneumoniae infection

Three cases of persistent bilateral sensorineural hearing loss following Mycoplasma pneumoniae (MP) infection are reported. These cases were characterized by highly elevated MP complement fixation titer and cold hemagglutinin titer. All the patients had bilateral acute otitis media with a moderate to high degree of mixed hearing loss in the early stage following primary atypical pneumonia (PAP).     

Immune-mediated disorders associated with idiopathic sudden sensorineural hearing loss

Different immune disorders are involved in the development of sudden sensorineural hearing loss (SSNHL). This includes a wide spectrum of immune-mediated disorders such as immune complexes, production of autoantibodies to the inner ear proteins, production of anticardiolipin (aCL) antibodies, and cellular immune defects. Some studies have also found an elevation of total IgE levels and a type 1 immune reaction. Our objective was to establish the association of "idiopathic" SSNHL (ISSNHL) with various autoantibodies, and to analyze the persistence over time of existing aCL and anti-beta2 glycoprotein 1 (anti-beta2 GP1) antibodies in such patients. Finally, we sought to establish a possible association between ISSNHL and total IgE elevation and whether this elevation is due to a specific type I immune reaction. In this prospective follow-up study, 51 patients considered as having ISSNHL were compared with 35 age-sex matched healthy volunteers over a 3-year period. All participants were tested for serum antinuclear antibodies, antithyroid antibodies, aCL, and rheumatoid factor. All patients who were positive for aCL antibodies were reanalyzed 3 months later for aCL antibody persistence and for the coexistence and persistence of anti-beta2 GP1 antibodies. Skin prick tests were performed in patients in whom total IgE was elevated. Antinuclear antibodies were positive in 9 of 51 (17%) and antithyroid antibodies in 11 of 51 (21%) ISSNHL patients, as compared to 1 of 35 (3%) and 2 of 35 (6%), respectively, in the control group. Rheumatoid factor was positive in 6 of the 51 patients (12%) and in none of the control group. Positive aCL antibodies were present in 16 of 51 patients (31%), 6 of whom (12%) were also positive for anti-beta2 GP1 antibodies. Three months later, aCL antibodies persisted in 7 patients (14%), and anti-beta2 GP1 in 4 patients. Only 2 of the normal subjects (6%) were positive for aCL antibodies, which persisted in only 1 of them (3%). The level of total IgE was elevated in 14 of 51 patients (27%), in contrast to 3 of 35 controls (8%). Six of them (42%) demonstrated a positive skin test to at least 1 allergen, but only 3 presented allergy symptoms. Our findings support the reported existence of multiple immune-mediated disorders in patients with ISSNHL. The lack of aCL antibody persistence in as many as half of our patients strongly suggests that transient phenomena (eg, viral infection) may trigger aCL antibody activity. However, the presence of aCL antibodies, especially in conjunction with anti-beta2 GP1 antibodies, suggests that in some patients, SSNHL is included among the rare symptoms of the antiphospholipid syndrome.