一个非综合征遗传性耳聋家系的遗传表型分析及致聋基因筛查

发布时间：2018-05-11 05:00

本文选题：遗传性耳聋 + 飞行时间质谱　；参考：《福建医科大学》2016年硕士论文

【摘要】：目的:通过对该非综合征性遗传性耳聋大家系的耳科及全身体格检查、听力学检测等资料的收集,探究该家系听力学及遗传学特点,并对部分家庭成员进行耳聋易感基因筛查。方法:对该家系成员进行详细家系调查,并对其中14名成员完成问卷调查、专科及全身体格检查和听力学检查,绘制家系遗传图谱,并完成该14名成员的血样采集及保存工作。通过仔细分析先证者父系及母系家系成员的临床表型及遗传学特征,分别预测其父系及母系家族可能存在的遗传方式,并对先证者致聋原因进行预测。同时结合飞行时间质谱技术对部分家族成员的样本进行检测分析,从而进行初步验证。结果:我们收集到一个来自福建省福清市的非综合症性遗传性耳聋家系。该大家系是因两位耳聋患者产生联姻关系而构成的大家庭,共84人,现存成员79人,采集血样14份。其中先证者父系(不包括先证者)现存40人,明确耳聋患者8人,发现听力异常的年龄从1岁至55岁不等。样本采集8份(听力正常2人,听力异常6人),其中4人表现为双侧极重度感音神经性耳聋;2人既往未察觉听力异常,经本次研究过程中对两人进行相关听力学检查后,发现不同程度听力下降。从第三代开始连续两代中均有发病患者,呈连续遗传现象;每一代成员中男女均可患病,子代患病个体的父母双方中至少一方为耳聋患者;第三代成员中,男性患者的后代中未发现耳聋患者,而女性患者的后代中发现耳聋患者。筛查4个常见致聋基因共20个位点,发现其中7份样本线粒体12S rRNA基因1555AG同质突变。先证者母系方(包括先证者在内)现存共39人,明确耳聋患者14人,发现听力异常年龄最小为6个月,最晚为56岁。样本采集6份,6名成员听力均异常,其中5人表现为先天性双侧极重度感音神经性耳聋即语前聋。从第三代开始连续三代中均有发病患者,呈连续遗传现象;每一代中男女均可患病,且子代患病个体的父母双方中,至少有一方为耳聋患者;若本人未患病时,即使其父母中有一方为耳聋患者,其子女也不会患病,则考虑其为常染色体显性遗传模式可能。筛查4个常见致聋基因共20个位点未发现突变位点。结论:1.通过先证者收集到一个因聋聋婚配产生联姻关系且具有不同遗传方式的非综合症性耳聋大家系,先证者父系表现为线粒体母系遗传模式;先证者母系成员表现为非综合症性常染色体显性遗传性耳聋;2.采用飞行时间质谱技术对样本进行筛查,检测4种致聋基因(GJB2、GJB3、SLC26A4及线粒体12sRNA)共20个基因位点,明确先证者父系为线粒体母系遗传性耳聋,包括先证者在内的母系成员初步排除几个已知基因致聋可能性。
[Abstract]:Objective: to investigate the characteristics of hearing mechanics and genetics in this family, and to screen some family members for susceptibility to deafness by collecting the data of general and general physical examination and audiological examination in this non-syndromic hereditary deafness department. Methods: the family members were investigated in detail, and 14 of them were investigated by questionnaire, physical examination and audiology examination, family genetic map was drawn, and the blood samples of 14 members were collected and preserved. By analyzing the clinical phenotypic and genetic characteristics of proband paternal and matrilineal family members, the possible genetic patterns of paternal and maternal families were predicted, and the causes of deafness in proband were predicted. At the same time, time-of-flight mass spectrometry was used to detect and analyze the samples of some family members. Results: we collected a non-syndromic hereditary deafness family from Fuqing City, Fujian Province. The family consisted of 84 persons, 79 extant members and 14 blood samples. There are 40 proband parents (excluding proband) and 8 deafness patients. The age of hearing abnormality is from 1 to 55 years old. 8 samples were collected (2 normal hearing and 6 abnormal hearing, 4 of them showed bilateral extremely severe sensorineural deafness and 2 had not detected abnormal hearing in the past. In the course of this study, two patients were examined by audiology. Different degrees of hearing loss were found. From the third generation, there are two consecutive generations of patients with disease, which is a continuous genetic phenomenon; each generation of members of men and women can be sick, at least one of the parents of the offspring of the individual with deafness; the third generation of members, No deafness was found in male offspring, while deafness was found in female offspring. A total of 20 loci were screened for 4 common deafness genes and 7 of them were found to have homogenous mutations in mitochondrial 12s rRNA gene 1555AG. A total of 39 proband (including proband) extant, 14 confirmed deafness, found that the minimum age of hearing impairment is 6 months, the latest 56 years old. All of the 6 members were found to have abnormal hearing, and 5 of them showed congenital bilateral extremely severe sensorineural deafness, that is, prelingual deafness. From the third generation, there are three consecutive generations of patients with disease, showing a continuous genetic phenomenon; each generation of men and women can be sick, and at least one of the parents of the offspring of the individual is deaf; if he is not ill, An autosomal dominant genetic model may be considered even if one of the parents is deaf and their children are not ill. No mutation loci were found in 20 loci of 4 common deafness genes. Conclusion 1. A non-syndromic deafness family with different genetic patterns was collected from the proband. The patrilineal pattern of the proband was mitochondrial maternal inheritance. The matrilineal members of the proband showed non-syndromic autosomal dominant hereditary deafness. Time of flight mass spectrometry (TF-MS) was used to screen the samples and to detect 20 loci of 4 deafness genes (GJB2GJB3SLC26A4 and mitochondrial 12sRNAs). It was clear that the paternal line of the proband was mtDNA hereditary deafness. Matrilineal members, including proband, initially excluded several known genes for deafness.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R764.43

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