摘要
目的分析云南省部分地区极重度非综合征型耳聋（non—syndromichearingloss，NSHL）患者常见耳聋基因GJB2和GJB3的突变特点，了解其分子流行病学特征。方法采集2010年1月一2013年12月我院门诊散发的118例极重度非综合征型感音神经性耳聋患儿和236例双亲外周血，提取DNA。应用飞行质谱技术对GJB2、GJB3编码区域中7个突变位点，包括GJB2（35delG、167delT、176—191dell6、235delc、299—300delAT），GjB3（538C—T、547G—A）进行检测，同时结合耳声发射、听性脑干反应测试、颞骨CT和头颅MRI检查。结果118例患儿中22例存在基因位点突变，占18．64％，其中235delC纯合突变8例，235delC单杂合突变6例，235delC／299—300delAT复合杂合突变8例；299—300delAT无纯合突变。未检出GJB3基因突变。236例双亲GJB2基因突变38例占16．10％，其中无235delC纯合突变，235delC单杂合突变父亲10例、母亲20例，299—300delAT单杂合突变父亲8例，299—300delAT无纯合突变，无235delC／299—300delAT复合杂合突变；未检出GJB3基因突变。结论云南省部分地区极重度非综合征型聋患儿GJB2突变率及突变形式与国内大部分报道基本一致，235delc是其最主要的突变形式，其次为299—300delAT。在以家庭为单位的耳聋基因筛查中，发现有基因突变患儿，对应其父母至少有一方存在基因突变，显示重要遗传特征。对于GJB3在云南地区的流行特征，有待进一步扩大研究GJB3的样本量。
Objective To analyze mutation features of common deafness genes GJB2 and GJB3 in patients with severe to profound non-syndromic sensorineural hearing loss in some areas of Yunnan Province. Methods 118 children with severe and profound non-syndromic sensorineural hearing loss sporadically identified in otological clinics and their parents （ n = 236） were included in this study. Their peripheral blood specimens were collected and DNA templates were extracted. MALDI-TOF-MS technology was used for detecting the seven mutation sites in coding region of GJB2 and GJB3, including GJB2 （35delG, 167delT, 176-191de116, 235delC, 299-300delAT）, and GJB3 （538C---~T, 547G--~A）. All of them received otoacoustic emission（ OAE）, auditory brainstem response（ ABR）, temporal bone CT and MRI scan. Results GJB2 gene mutations were confirmed in 22 of the 118 children （n = 22, 18.64% ）, including 235delc homozygous mutation （n = 8 ）, 235delC single heterozygosity mutation （n = 6）, 235delC/299-300delAT double heterozygosity mutation （n = 8）. 299-300del AT homozygous mutation could not be detected. GJB3 mutation was not found. In the 236 parents, GJB2 gene mutations were confirmed in 38 （16. 10% ）including 235delC single heterozygosity mutation （Fn = 10, Mn = 20）, 299-300del AT a single heterozygosity mutation （Fn = 8）. GJB3 gene mutation was not detected. Conclusions GJB2 mutation rate and mutant forms in children with severe and profound non-syndromic sensorineural deafness in Yunnan are consistent with most of the domestic literature reports. 235de1C is the main mutant form, followed by the 299-300delAT mutation. Deafness genes screening based on family unit finds that gene mutations exist in at least one person of the spouse whose child has gene mutations.
出处
《中国耳鼻咽喉颅底外科杂志》
CAS
2015年第2期99-103,共5页
Chinese Journal of Otorhinolaryngology-skull Base Surgery
基金
云南省科技厅和昆明医科大学联合专项(2012FB110)
云南省科技厅应用基础研究项目(2013FZ243)
