常染色体显性遗传非综合征型耳聋家系的遗传学特征分析

Genetic analysis in a Chinese family with autosomal dominant nonsyndromic deafness

目的研究一个连续5代遗传的耳聋大家系(Z029家系),分析该家系的遗传学特征。方法利用解放军总医院耳鼻咽喉研究所遗传性耳聋资源收集网络采集到一个5代遗传性耳聋大家系,对具有遗传信息的47例成员进行了全身系统检查及临床听力学检测,应用Cyrillic2.1软件构建家系图谱,分析该家系的遗传学特征。结果Z029家系的表型表现为全频听力下降为主、迟发型的感音神经性耳聋,连续5代发病,男女成员均受累,每代患者的比率随着年龄增长具有逐渐增加的趋势,符合延迟显性的特征。结论Z029家系是一个非综合征型常染色体显性遗传性耳聋大家系,其表型的外显率与年龄相关。该研究为进一步的致病基因定位与克隆奠定了基础,并为与年龄相关性耳聋分子病理机制的研究提供了模板。

Objective To analyze and determine the genetic characteristics of a large Chinese family with autosomal dominant nonsyndrornic deafness （named pedigree Z029）. Methods A hereditary deafness family was found from the profuse genetic resource established in the Otolaryngology Institute of PLA General Hospital. A sequence of bilateral sensorineural heating impairment transmitted through five generations was found by investigating 47 individuals in the pedigree. The genetic forms of hearing loss in 18 members of the Z029 pedigree were diagnosed by otologic, audiologic, and physical examination, as well as by the study on their family history. Pedigree map was drown by using Cyrillic2. 1 software.Results The phynotype of Z029 family showed that most affected individuals had sensorineural hearing impairment with subsequent gradual progression covering all frequencies. The phynotype was transmitted from 1 to 5 generations. One of the parents of every patient was definitely a patient of the same disease. The affected ratio was same in both sexes, and the incidence of deafness declined through the first to fifth generation. Conclusion The phenotype characteristics of Z029 family were of autosornal dominant nonsyndromic hereditary deafness. In this pedigree, hearing impairment occurred in the majority of affected individuals after their twentieth year of age, and the penetmnce of the impairment appeared to be age-correlated. No obvious vestibular dysfunction and other associated abnormalities were found. It may provide a foundation for the study of gene mapping and gene cloning of the pathogenic gene to analyze and determine the phenotype characteristics of this pedigree. This pedigree also provided an excellent model for the further study on the pathological and molecular mechanisms of hereditary hearing impairment related to age.