论文部分内容阅读
目的分析一个迟发性常染色体遗传性聋大家系的表型特征,并进行候选致病基因筛查。方法对门诊发现的1例迟发性渐进性感音神经性聋患者进行家系调查、病史资料采集、常规检查、听力学及前庭功能检查。听力学检查包括纯音测听、声导抗、耳声发射。先证者进行颞骨CT扫描。绘制家系图,进行遗传方式分析。采集家系成员外周血DNA,采用聚合酶链反应(polymerase chain reaction,PCR)扩增,对已知的常染色体显性遗传性聋的致病基因GJB3、COCH、KCNQ4等22个基因附近的遗传标记与疾病进行连锁分析,对GJB2基因同时进行了全部编码序列突变检测。结果该家系共6代81人,现存4代71人,主诉听力障碍者14人,其先证者诊断为感音神经性聋,遗传特点为代代相传、男女都发病,符合常染色体显性遗传方式,听力表型为一种迟发型的、渐进性的、先以高频下降为主后累及全频的感音神经性听力损失,听力曲线呈下降型。GJB2基因全部编码序列未发现突变,连锁分析显示:GJB3、COCH、KCNQ4等22个基因附近的遗传标记与疾病不连锁。结论已知的常染色体显性遗传性聋的致病基因与该家系耳聋不连锁,可能不是其致病基因。该家系耳聋可能由一个新的致聋基因所致。为了寻找到该家系的致聋基因,下一步将进行全基因组扫描、连锁分析、定位克隆研究。
Objective To analyze the phenotypic characteristics of a late-onset autosomal dominant deafness pedigree and to screen for candidate pathogenic genes. Methods One case of delayed onset sensorineural deafness found in outpatient department was investigated by family history, history data collection, routine examination, audiology and vestibular function. Audiology including pure tone audiometry, acoustic impedance, otoacoustic emissions. Provisional who CT scan of the temporal bone. Draw family diagram, genetic analysis. Genomic DNA was extracted from peripheral blood of family members and amplified by polymerase chain reaction (PCR). Genetic markers such as GJB3, COCH and KCNQ4, which are known to be associated with autosomal dominant deafness, Linkage analysis with the disease, the GJB2 gene at the same time all the mutations in the coding sequence detection. Results The pedigree had a total of 6 generations of 81 people, the existing 4 generations of 71 people, chief complaint of 14 people with hearing impairment, the proband was diagnosed as sensorineural deafness, genetic characteristics from generation to generation, both men and women, consistent with autosomal dominant Hereditary, audiographic phenotype is a late-onset, progressive, first with high-frequency descent after the main frequency-sensitive neurological hearing loss, hearing loss curve was descending. No mutations were found in the entire coding sequence of GJB2 gene. Linkage analysis showed that the genetic markers near 22 genes such as GJB3, COCH and KCNQ4 were not linked to the disease. Conclusions The known genetic pathogenicity of autosomal dominant deafness is not linked with deafness of this pedigree, and may not be the causative gene. Deafness in the family may be caused by a new deafness gene. In order to find the family of deafness genes, the next step will be genome-wide scanning, linkage analysis, positioning cloning.