Li Yan-hua, Jiang Hua, Yang Li-juan, Xu Hong-Xia, Li Hui, Li Hui-wu, Luo Yong-hai, Wang Chang-wei, Zou Guang-hua
Department of Otorhinolaryngology, Xinjiang Medical University, Urumqi 830000, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2010 Aug;45(8):645-51.
To study mtDNA, GJB2, GJB3 and determine gene mutation situs and frequency in Uighur and Han people with hereditary nonsyndromic hearing loss, and to compare the differences of gene mutation situs and frequency between Uighur and Han people.
Blood samples were obtained from 93 patients (43 Uygur and 50 Han) with hereditary non-syndromic hearing loss and 110 normal people (56 Uygur and 54 Han). Genomic DNA was extracted from isolated leukocytes, and amplified by polymerase chain reaction (PCR). PCR products of GJB3 were sequenced directly; while PCR products of mitochondrial DNA 12S rRNA A1555G point mutations were analyzed by PCR-Alw26I digestion, and positive ones were further sequenced. GJB2 genes of 83 patients (43 Uygur and 40 Han) with hereditary non-syndromic hearing loss and 98 normal people (46 Uygur and 52 Han) were directly sequenced.
Among GJB3 genes of 93 patients, 2 cases of 33C-T, 2 cases of of 766G-A, 7 cases of 357C-T, and 4 cases of 798C-T were detected. Mitochondrial DNA 12SrRNA A1555G mutation was detected in 8 patients (2 Uygur and 6 Han). Nine kinds of base changes of GJB2 were detected: 109G-A, 233-235delC, 79G-A, 196G-A, 341A-G, 564G-A, 380G-A, 71G-A, and 35delG. In the control group, detected GJB3 mutations included 4 cases of 357C-T, 5 cases of 798C-T, and 2 cases of 93C-T; while 9 kinds of base changes of GJB2 were detected: 341A-G, 380G-A, 457G-A, 79-GA, 109G-A, 281A-G, 21G-T, 171G-T, and 368C-A. For mtDNA 12SrRNA A1555G, the difference between study group of and control group of Han people was statistically significant (P < 0.05). For GJB2 mutation 79G-A, the difference between study group and control group was statistically significant (P < 0.05) in both Uygur and Han people; while for GJB2 mutation 341A-G, the difference in study group between Uygur and Han people was statistically significant (P < 0.05). And for GJB3 mutation 798C-T, the difference was statistically significant both between study group and control group, and between Uygur and Han people (P < 0.05).
In Xinjiang, mutation rate was high for mtDNA 12SRNA A1555G. while GJB3 gene mutations were not the main cause of the hereditary nonsyndromic hearing loss. There were certain ethnic and geographical characteristics of GJB2and GJB3 mutations.
研究线粒体DNA（mtDNA）、缝隙连接蛋白2（GJB2）、缝隙连接蛋白3（GJB3）基因，确定新疆维吾尔族和汉族遗传性非综合征性听力损失患者的基因突变位点及频率，并比较两民族基因突变位点及频率的差异。
收集93例遗传性非综合征性听力损失患者（维吾尔族43例，汉族50例）及110例正常人（维吾尔族56例，汉族54例）的血样。提取外周血白细胞基因组DNA，采用聚合酶链反应（PCR）扩增。GJB3基因PCR产物直接测序；线粒体DNA 12S rRNA A1555G点突变采用PCR-Alw26I酶切分析，阳性产物进一步测序。对83例遗传性非综合征性听力损失患者（维吾尔族43例，汉族40例）及98例正常人（维吾尔族46例，汉族52例）的GJB2基因进行直接测序。
93例患者的GJB3基因中，检测到33C-T突变2例、766G-A突变2例、357C-T突变7例、798C-T突变4例。线粒体DNA A1555G突变在8例患者中检测到（维吾尔族2例，汉族6例）。GJB2基因检测到9种碱基改变：109G-A、233-235delC、79G-A、196G-A、341A-G、564G-A、380G-A、71G-A、35delG。对照组GJB3基因检测到357C-T突变4例、798C-T突变5例、93C-T突变2例；GJB2基因检测到9种碱基改变：341A-G、380G-A、457G-A、79-GA、109G-A、281A-G、21G-T、171G-T、368C-A。汉族研究组与对照组线粒体DNA A1555G突变差异有统计学意义（P<0.05）。维吾尔族和汉族研究组与对照组GJB2基因79G-A突变差异均有统计学意义（P<0.05）；维吾尔族和汉族研究组GJB2基因341A-G突变差异有统计学意义（P<0.05）。GJB3基因798C-T突变在研究组与对照组间、维吾尔族与汉族间差异均有统计学意义（P<0.05）。
新疆地区线粒体DNA A1555G突变率较高，GJB3基因突变不是遗传性非综合征性听力损失的主要原因。GJB2和GJB3基因突变具有一定的民族和地域特征。
