广西地区先天性心脏病高发家系遗传学分析

发布时间：2018-05-16 07:44

本文选题：先天性心脏病 + 高发家系　；参考：《广西医科大学》2012年硕士论文

【摘要】：背景：先天性心脏病(Congenital heart disease, CHD)为一种血液循环结构和功能的畸形,即可在刚出生时被检查出,也可以在以后生活中被发现,是世界上新生儿先天性缺损和导致新生儿显著死亡率的最常见类型。大多数CHD畸形的原因仍然未知,但基因遗传因素被认为扮演重要的角色。大多数CHD患者都零散出现在家族中,病因至今不明。诊断和治疗治疗主要基于解剖和生理因素,随着儿童心脏保健的不断发展,大多数婴幼儿可以通过儿科手术修复并且恢复良好,降低了CHD患者的死亡率。但对于CHD潜在病因知识的缺乏大大降低了对CHD预防和改变疾病发生的能力,从而阻碍了预防和早期治疗策略的发展。流行病学研究已经表明CHD复发高风险多为先证者的兄弟姐妹和后代,CHD家族聚集复发率为2-4%,随着现代遗传分析技术的发展,CHD不在受限于基因序列或基因鉴定能力,但达到成功的研究需要有三个预备知识或先决条件：1.丰富的显形案例2.一个遗传学固定框架3.健全的研究设计。所以积极达到需要条件后,通过遗传分析技术找到CHD的发病原因作为CHD实验研究与临床治疗方向。但目前国内关于CHD的高发家系的显形案例和血液标本少,不能达到检测CHD相关基因筛查的目标,所以现在的任务是收集大量CHD高发家系的显形案例和建立血液标本库,为下一步CHD的基因筛查打下基础。目的：对广西地区CHD患者进行筛查,分析近2年广西地区CHD家族聚集情况,整个家系中出现不少于2例(2例及2例以上) CHD患者的家系称为高发家系,并收集高发家系先证者及其一、二级亲属血液标本,建立血液标本库；对高发家系进行遗传学分析,进一步研究CHD的临床特点和遗传方式,为CHD基因研究提供基础。方法：对广西医科大学第一附属医院小儿科、心胸外科住院治疗CHD患者进行逐个调查,成员包括先证者、及其一级亲属、二级亲属,收集CHD患者及其家系的资料,填写CHD核心高发家系登记表,绘制家系图谱,并采集先证者及其父母血液标本；对于高发家系,对先证者一、二级亲属中患CHD者填写CHD核心高发家系登记表,可疑者由内科专家检查并做心脏彩色B超等辅助检查,确诊后采集其亲属家系成员血液标本,进而对高发家系进行遗传性分析。结果：2009年10月至2011年11月共收集140例CHD先证者,其中高发家系49例。把高发家系中先证者患病种类按传统分类法分成13种,为室间隔缺损(Ventricular septal defect, VSD)、房间隔缺损(Atrial septal defect, ASD)、法洛四联症(Tetralogy of Fallot, TOF)、房室间隔缺损(Atrio-Ventricular septal defect,AVSD)等。49例高发家系中,一级亲属和二级亲属CHD总患病率为6.29%(71/779),其中一级亲属的患病率为20.60%(41/199),二级亲属为5.00%(30/580),一、二级亲属患病率比较,差异有统计学意义(X2=42.59,P0.001)。在49例高发家系中,父亲既抽烟又喝酒占19例,母亲孕前妊娠期用药者占19例。在高发家系中有5例代表性典型病例,为发病例数最多的家系,ASD、VSD、AVSD同时存在的家系,一、二级亲属中都有CHD患者家系,与性别相关的CHD家系,只有AVSD存在的家系；140例先证者中有2例合并心外畸形(CHD合并六指畸形和CHD合并耳畸形),但不属于高发家系。结论：广西地区CHD家系调查中有家族聚集现象；先证者亲属的发病率高低与先证者血缘关系近远有相关性,其发病率高低依次为先证者的一级亲属、二级亲属；遗传学分析显示,CHD符合多基因遗传方式；49例高发家系先证者CHD类型构成比最高的为VSD；外界环境因素也是先证者CHD发生的重要因素,如母亲孕前和妊娠期细菌病毒感染史,父母孕前和妊娠期用药史,父母吸烟史和喝酒史等。CHD合并发生心外畸形的可能性大(六指畸形,耳畸形)。
[Abstract]:Background : Congenital heart disease ( CHD ) is a kind of deformity of blood circulation structure and function . It can be checked out at birth . It is the most common type of congenital defects in the world .

Objective : To screen the CHD patients in Guangxi region , and analyze the aggregation of CHD family in Guangxi region in recent 2 years . There are not less than 2 cases in the whole family ( 2 cases and more than 2 cases ) .

The family of CHD patients is called high - hair family , and the blood samples of first and second - degree relatives of high - hair families are collected , and blood sample banks are established .
In order to provide the basis for the study of CHD gene , genetic analysis of high - hair family was carried out .

Methods : A case - by - case study of CHD patients was carried out in the first Affiliated Hospital of Guangxi Medical University . The members included the proband , their first relatives , the second relatives , the data collected from CHD patients and their families , completed the registration form of CHD core , mapped the family map , and collected the first proband and their parents ' blood specimens .
For the high incidence family , the CHD patients in the first and second relatives of the proband are filled with the CHD core high - risk family registration form . The suspicious persons are examined by the medical experts and subjected to auxiliary examination such as heart color Doppler ultrasound . After the diagnosis , the blood samples of the relatives of their relatives are collected , and then genetic analysis is carried out on the high - hair families .

Results : From October 2009 to November 2011 , 140 CHD probands were collected , including 49 cases with high incidence . Among them , the prevalence rate of first - degree relatives and second - degree relatives was 6.29 % ( 71 / 779 ) . Among them , the prevalence of first - degree relatives and second - degree relatives was 6.29 % ( 71 / 779 ) , and the prevalence of first - degree relatives was 20.60 % ( 41 / 199 ) . Among the 49 high - hair families , there were 19 cases of father ' s smoking and alcohol drinking , 19 cases of pregnant women before pregnancy . There were 5 representative cases in the family of high incidence . Among them , there were five representative cases in the family of high incidence , the family of ASD , VSD , AVSD , the family of CHD patients , the family of CHD patients with sex , and only AVSD ' s family .
Among the 140 probands , there were 2 cases of congenital anomaly ( CHD with six finger deformity and CHD combined ear deformity ) , but it was not belong to the high incidence family .

Conclusion : There are family aggregation in CHD family in Guangxi .
The incidence of the relatives of the probands is closely related to the blood relationship of the proband , the incidence of which is the first - degree relatives and the second - degree relatives of the probands in turn .
Genetic analysis showed that CHD was consistent with multi - gene inheritance .
Among the 49 patients with high incidence of CHD , CHD type was higher than that of VSD ;
The external environmental factors are important factors of CHD , such as the history of pre - maternal and pregnancy bacterial infection , the history of pre - pregnancy and pregnancy , smoking history of parents and the history of drinking alcohol .

【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.4

【参考文献】