本文選題：基因　切入點(diǎn)：家族性　出處：《貴州醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討家族性高膽固醇血癥(familial hypercholesterolemia,FH)的分子病理機(jī)制,分析FH患者基因突變位點(diǎn)與臨床表型之間的關(guān)系。方法:以一FH家系為研究對象,對其成員進(jìn)行體格檢查及血脂、心電圖、心血管超聲等檢查。運(yùn)用聚合酶鏈?zhǔn)椒磻?yīng)(polymerase chain reaction,PCR)擴(kuò)增部分成員LDL-R基因啟動子和18個(gè)外顯子,測序后與GenBank中正常基因比對,確認(rèn)是否存在突變。同時(shí)檢測ApoB100基因,除外家族性載脂蛋白B100缺陷癥(familial defective apolipoprotein B,FDB)。結(jié)果:共調(diào)查該家系3代8人。先證者父母為近親結(jié)婚。其中7人診斷為FH患者,血清總膽固醇分別為18.98、8.69、7.51、7.36、11.64、9.24、9.57mmol/L(正常值:2.80~5.20mmol/L),臨床診斷先證者為FH純合子型,其余成員均為FH雜合子型。DNA測序排除該家系A(chǔ)poB100基因突變,而先證者LDL-R基因第2號外顯子第97位編碼堿基存在堿基置換(CT),導(dǎo)致終止密碼子在第12位提前出現(xiàn),發(fā)生Q12X突變改變,基因型為TT純合子;其父親、母親及胞弟均為攜帶Q12X突變的雜合子。結(jié)論:1.先證者及其胞弟、父、母、祖母、外祖母、二叔臨床表現(xiàn)、體格檢查、血脂測定及超聲檢查均支持FH診斷,且先證者已達(dá)到臨床診斷FH純合子標(biāo)準(zhǔn),多數(shù)成員存在不同程度的動脈硬化;2.該家系A(chǔ)poB100基因無突變,排除FDB的可能;3.先證者及其父母、胞弟LDL-R基因均存在Q12X突變,為終止突變,為該FH家系發(fā)病的分子基礎(chǔ);4.FH臨床表現(xiàn)各不相同,受基因和環(huán)境因素共同作用。
[Abstract]:Objective: to investigate the molecular pathological mechanism of familial hypercholesterolemia (FH) and to analyze the relationship between gene mutation site and clinical phenotype in FH patients. Electrocardiogram, cardiovascular ultrasound and so on. The promoter and 18 exons of LDL-R gene were amplified by polymerase chain reaction polymerase chain reaction (PCR). After sequencing, they were compared with the normal gene in GenBank to confirm the existence of mutation. At the same time, the ApoB100 gene was detected. Results: a total of 3 generations of 8 people from this family were investigated. The proband parents were married to their close relatives. Seven of them were diagnosed as FH patients. The serum total cholesterol was 18.988 / 8.69 / 7.51 / 7.36 / 11.64 / 9.24 / 9.57 mmol / L (normal value: 2.80 / 5.20 mmol / L). The proband of clinical diagnosis was FH homozygous type, and the other members were FH heterozygote type. DNA sequencing excluded the mutation of ApoB100 gene in this family. The nucleotide substitution of the nucleotide sequence at 97 of exon 2 of the LDL-R gene in the proband led to the early emergence of the termination codon at the 12th position and the mutation of Q12X. The genotype was TT homozygote. Both mother and brother were heterozygous with Q12X mutation. Conclusion: 1. The proband and his brother, father, mother, grandmother, grandmother, second uncle clinical manifestation, physical examination, blood lipids test and ultrasonic examination all support the diagnosis of FH. Moreover, the proband had reached the standard of clinical diagnosis of FH homozygote, and most of the members had different degrees of arteriosclerosis 2.There was no mutation in the ApoB100 gene of this pedigree and the possibility of excluding FDB was excluded. The proband and his parents and siblings had Q12X mutation in the LDL-R gene, which was a termination mutation. 4. The clinical manifestations of FH were different and affected by gene and environmental factors.
【學(xué)位授予單位】：貴州醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.2

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