遗传 ›› 2006, Vol. 28 ›› Issue (12): 1489-1489~1494.doi: 10.1360/yc-006-1489

• 研究报告 • 上一篇    下一篇

常染色体显性遗传非综合征性耳聋致病基因定位研究

孙悍军1,3, 陶 然2, 程 静1,4, 杨淑芝1, 曹菊阳1, 于黎明1, 洪梦迪1, 冯国鄞2, 戴 朴1, 袁慧军1, 韩东一1, 贺 林2
  

  1. (1. 解放军总医院耳鼻咽喉头颈外科, 解放军总医院耳鼻咽喉研究所, 北京 100853; 2. 上海交通大学Bio-X生命科学研究中心,
    上海 200030; 3. 武警总医院耳鼻咽喉头颈外科, 北京 100039; 4. 四川大学生命科学学院, 成都 610064)

  • 收稿日期:2006-07-25 修回日期:2006-09-08 出版日期:2006-12-10 发布日期:2006-12-10
  • 通讯作者: 贺 林

Mapping of Gene Underlying Autosomal-dominant Non-syndromic Hearing Loss(DFNA)

SUN Han-Jun1, 3, TAO Ran2, CHENG Jing1, 4, YANG Shu-Zhi1, CAO Ju-Yang1, YU Li-Ming1,
HONG Meng-Di1, FENG Guo-Yin2   

  1. (1. Department of Otolaryngology Head and Neck Surgery, PLA General Hospital, Beijing 100853, China;
    2. Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai 200030, China;
    3. Department of Otolaryngology Head and Neck Surgery, The General Hospital of Chinese Peoples Armed Policed, Beijing 100039, China; 4. Life Science Center, Sichuan University, Chengdu 610064, China)
  • Received:2006-07-25 Revised:2006-09-08 Online:2006-12-10 Published:2006-12-10
  • Contact: HE Lin

摘要:

耳聋具有高度的遗传异质性, 迄今已定位了51个常染色体显性遗传非综合征型耳聋(autosomal dominant non-syndromic sensorineural hearing loss, DFNA)基因位点, 20个DFNA相关基因被克隆。文章收集了一个DFNA巨大家系, 家系中有血缘关系的家族成员共170人, 对73名家族成员进行了详细的病史调查、全身检查和耳科学检查, 提示39人有不同程度的迟发性感音神经性听力下降, 未见前庭及其他系统的异常。应用ABI公司382个常染色体微卫星多态标记进行全基因组扫描连锁分析, 将该家系致聋基因定位于14q12-13处D14S1021-D14S70之间约7.6 cM (3.18 Mb)的区域, 最大LOD值为6.69 (D14S1040), 与已知DFNA9位点有4.7 cM (2.57 Mb)的重叠区, DFNA9致病基因COCH位于重叠区域内。下一步拟进行COCH基因的突变筛查, 以揭示该家系耳聋的分子致病机制。

关键词: 连锁分析, 基因定位, DFNA9, 耳聋

Abstract:

Hereditary non-syndromic sensorineural hearing loss is a genetically highly heterogeneous group of disorders. To date, at least 50 loci for autosomal dominant non-syndromic sensorineural hearing loss (DFNA) have been identified by linkage analysis. Here we report a huge family with late onset autosomal dominant hereditary non-syndromic hearing loss. In this family, 73 of 170 family members have been conducted physical examination, pure-tone audiometry, immittance testing and auditory brainstem response testing (ABR). The results indicated that 39 of 73 tested family members have sensorineural hearing loss in various degrees. No associated visible abnormalities in other systems were found in this family. After exclusion of the 14 known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 382 highly informative microsatellite markers at approximately 9.2 cM intervals throughout the genome. Linkage analysis was carried out under a fully penetrant autosomal dominant mode of inheritance with no phenocopies. A maximum two-point LOD score of 6.69 at theta=0 was obtained for marker D14S1040. Haplotype analysis placed the locus within a 7.6 cM genetic interval defined by marker D14S1021 and D14S70, overlapping with the DFNA9 locus.

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