Otopathology in Mohr-Tranebjaerg syndrome
Otopathology in Mohr-Tranebjaerg syndrome
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DOI：
10.1097/mlg.0b013e3180581944
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发表时间：
2007-07-01
期刊：
影响因子：
2.6
通讯作者：
Tranebjaerg, Lisbeth
中科院分区：
文献类型：
--
作者：
Bahmad, Fayez, Jr.;Merchant, Saumil N.;Tranebjaerg, Lisbeth
背景资料：Mohr-Tranebjgaerg综合征（MTS）是一种X连锁隐性综合征性感音神经性听力损失（HL），其特征是儿童期耳聋，随后在成年后发生影响大脑和视神经的进行性神经变性。MTS是由DDP/TIMM 8A基因突变引起的，该基因编码97个氨基酸的多肽;该多肽是线粒体内膜的转位酶。目的：描述四个患有MTS的个体的耳病表现和颞骨组织病理学。材料和方法：所有四名受试者都属于一个多代挪威大家庭，并且已知在TIMM 8A基因中携带移码突变。在尸检时取出颞骨，并通过光学显微镜进行研究。耳蜗毛细胞，血管纹，耳蜗神经元细胞。还对前庭神经元进行了计数。结果：所有四名受试者都在幼儿期出现了进行性HL，到10岁时变得严重耳聋。这四个人都发展了语言，至少有一个人在早期生活中使用了扩音器。两名受试者的听力评估显示，到10岁时，HL为80- 100 dB。受试者在49岁至67岁之间死亡。耳病理学是惊人的相似，所有的骨骼检查显示耳蜗神经元细胞几乎全部损失和前庭神经元的严重损失。当与年龄匹配的对照组相比，有90%至95%的损失耳蜗神经元和75%至85%的损失前庭neurons.Conclusions：我们推断，在MTS的HL可能是一个出生后和进行性退化的耳蜗神经元和MTS构成一个真正的听神经病的结果。我们的研究结果对MTS患者的临床诊断和HL的管理具有重要意义。
Background: Mohr-Tranebjgaerg syndrome (MTS) is an X-linked, recessive, syndromic sensorineural hearing loss (HL) characterized by onset of deafness in childhood followed later in adult life by progressive neural degeneration affecting the brain and optic nerves. MTS is caused by mutations in the DDP/TIMM8A gene, which encodes for a 97 amino acid polypeptide; this polypeptide is a translocase of the inner mitochondrial membrane.Objectives: To describe the otologic presentation and temporal bone histopathology in four affected individuals with MTS.Material and Methods: All four subjects belonged to a large, multigenerational Norwegian family and were known to carry a frame shift mutation in the TIMM8A gene. Temporal bones were removed at autopsy and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria vascularis, and cochlear neuronal cells. Vestibular neurons were also counted.Results: All four subjects developed progressive HL in early childhood, becoming profoundly deaf by the age of 10 years. All four developed language, and at least one subject used amplification in early life. Audiometric evaluation in two subjects showed 80- to 100-dB HL by the age of 10 years. The subjects died between the ages of 49 and 67. The otopathology was strikingly similar in that all bones examined showed near-total loss of cochlear neuronal cells and severe loss of vestibular neurons. When compared with age-matched controls, there was 90% to 95% loss of cochlear neurons and 75% to 85% loss of vestibular neurons.Conclusions: We infer that the HL in MTS is likely to be the result of a postnatal and progressive degeneration of cochlear neurons and that MTS constitutes a true auditory neuropathy. Our findings have implications for clinical diagnosis of patients with MTS and management of the HL.