Joint Study on Genetic Analysis of Hereditary Hearing Loss

遗传性听力损失遗传分析的联合研究

• 批准号: 07044215
• 负责人: SHINKAWA Hideichi
• 金额: $ 2.05万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044215/
• 关键词: hearing loss; genetics; mitochondrial DNA; recessive; (遺伝性)難聴; 遺伝子

Joint Study on Genetic Analysis of Hereditary Hearing LossMitochondrial mutations are known to be one of the causes of non-syndromic sensorineural hearing loss (SNHL). Among them, a 1555A->G mutation has been reported to cause susceptibility to aminoglycoside antibiotics. In the present study, thirteen Japanese families showing 1555A->G mutation were genetically as well as clinically investigated. The regional predominance has lead us to examine the evolution of mutant mitochondrial DNA by comparing polymorphisms found in different Japanese families. Restriction enzyme analysis revealed several polymorphisms of mtDNA in these pedigrees. No specific mutation having a possible relation to hearing impairment except for 1555A->G was found among the mutations studied. The D-loop sequence together with the mtDNA RFLP variation and 9 bp deletion showed identical patterns regarding mutations between the three families, indicating that each group may possibly have had a common ancestor. Many su … More bjects who harbor this mitochondrial mutation exhibit a mild, high frequency, progressive hearing loss even without aminoglycoside injection. Regardless of amminoglycoside exposure, hearing loss was usually associated with permanent tinnitus. The results presented here appear to support the hypothesis that the A 1555G mutation may play a more general role in causing hearing loss.Hereditary hearing loss patients whose inheritance seems to be autosomal recessive in Aomori Prefecture (Northern Japan) were surveyed. Three phenotypically distinct categories of recessive hearing loss, profound, high frequency, and moderate, could be identified. The most common type, which is high frequency progressive hearing loss seems to be somewhat unique in this area, suggestiong a new gene may be involved.We describes three familial cases of recessive hereditary hearing loss associated with enlargement of the vestibular aqueduct (EVA). These cases suggested EVA may be a useful discriminator between different types of recessive hearing loss. We are currently searching the responsible gene for this type of hearing loss. Less

遗传性耳聋遗传分析的联合研究线粒体突变是引起非综合征型感音神经性耳聋（SNHL）的原因之一。其中，1555 A->G突变已被报道导致对氨基糖苷类抗生素的敏感性。在本研究中，13个日本家庭显示1555 A->G突变的遗传以及临床调查。区域优势使我们研究突变线粒体DNA的进化，通过比较在不同的日本家庭中发现的多态性。限制性内切酶分析显示，这些家系的线粒体DNA的几个多态性。除1555 A->G突变外，未发现与听力损伤相关的特异性突变。D-loop序列与mtDNA RFLP变异和9 bp缺失显示三个家族之间的突变模式相同，表明每个群体可能有一个共同的祖先。许多苏 ...更多信息 携带这种线粒体突变的人即使不注射氨基糖苷类也表现出轻度、高频率、进行性听力损失。无论是否暴露于氨基糖苷类药物，听力损失通常与永久性耳鸣相关。本研究的结果似乎支持这一假设，即A 1555 G突变可能在导致听力损失中发挥更普遍的作用。对青森县（北方日本）的遗传性听力损失患者进行了调查，这些患者的遗传似乎是常染色体隐性遗传。隐性听力损失有三种不同的表型，即深度、高频和中度。最常见的一种是高频进行性听力损失，它在这一领域似乎有些独特，但可能涉及一个新的基因。提示伊娃可作为不同类型隐性听力损失的一种有效鉴别方法。我们目前正在寻找这种类型的听力损失的责任基因。少

项目成果

Usami,S.,Abe,S.,Shinkaw,H.,Moeller,B.,Kenyon,JB.,Kimberling,WJ.: "Genetic and Clinical Features of SNHL associated with the 1555 mitochondrial mutation" Laryungoscope. (発表予定).

Usami, S.、Abe, S.、Shinkaw, H.、Moeller, B.、Kenyon, JB.、Kimberling, WJ.：“与 1555 线粒体突变相关的 SNHL 的遗传和临床特征”（即将提交） ）。

Abe, S.et al.: "Three familial cases of non-syndromic hereditary hearing loss associated with the enlargol vestibular aqueduct" Annals of Otol.Rhinol.Laryngol.(in press).

Abe, S.等人：“与 enlargol 前庭导水管相关的三例非综合征性遗传性听力损失家族病例”Otol.Rhinol.Laryngol 年鉴（正在出版）。

S Abe,S Usami,H Shinkawa: "Three familial cases of non-syndromic hereditary hearing loss associated with the enlarged vestibular aqueduct" Annals of Otology,Rhinology&Laryngology. (in press).

S Abe、S Usami、H Shinkawa：“与前庭导水管扩大相关的非综合征性遗传性听力损失的三例家族病例”耳科、鼻科年鉴