發(fā)布時間：2018-04-14 03:06

  本文選題：心肌病 + 肥厚型�。� 參考：《鄭州大學》2017年碩士論文

【摘要】：背景肥厚型心肌病(HCM)是最常見的遺傳性心臟病,具有顯著的遺傳異質性。對HCM的認識已逾50年,最近在HCM診斷和治療方面取得了實質性的進展,臨床實踐中對本病的認識也隨之提高。目前已發(fā)現(xiàn)至少27個HCM致病基因,超過1500個突變與HCM相關。國內對HCM的致病基因的研究多局限于數個編碼肌小節(jié)的基因,這必然導致致病基因的檢出率降低,使一部分攜帶其他致病基因HCM病例篩查不出致病基因,對其家系成員的篩查及遺傳學研究也就無從談起。目的利用新一代高通量測序技術(NGS)對人心肌病相關的靶基因組的44個基因全測序,并分析基因突變的特點以及基因型及臨床表型的關系。方法納入2012-2016年就診于河南省胸科醫(yī)院的家族性肥厚型心肌病(FHCM)先證者15名,搜集臨床資料(包括病史、體格檢查、心臟彩超、心電圖),全面篩查44個人泛心肌病靶基因。對基因篩查陽性的先證者,應用Sanger測序檢測家系中其他成員的特定基因。對新發(fā)現(xiàn)的突變基因,通過Poly Phen-HCM及不同物種的蛋白序同源性對比確定其致病性,并與健康對照組進行對比,最后對致病性突變攜帶者進行基因型及臨床表型相關性的分析。結果入組的15名肥厚型心肌病先證者中,在8位先證者發(fā)現(xiàn)了HCM 5個相關致病基因的9種突變,其中1例為雙基因突變,2例為新發(fā)現(xiàn)的突變,國內外均未見報道。結論1.MYBPC3基因9號外顯子c.903del G突變以及MYBPC3基因26號外顯子c.2834GA突變國內外均未見報道,為新發(fā)現(xiàn)的致病性突變。MYBPC3基因c.903del G突變臨床表型嚴重,易于發(fā)生惡性心率失常,治療上需要采取更積極的措施;MYBPC3基因26號外顯子c.2834GA突變臨床表型具有多樣性。2.在家系遺傳的基礎上可以發(fā)生從頭突變,雙突變攜帶者發(fā)病早,心肌肥厚程度重,臨床表現(xiàn)較重,預后較差。
[Abstract]:Background HCM (hypertrophic cardiomyopathy) is the most common hereditary heart disease with significant genetic heterogeneity.HCM has been recognized for more than 50 years. Recently, substantial progress has been made in the diagnosis and treatment of HCM, and the understanding of the disease has also been improved in clinical practice.At least 27 HCM genes have been identified and more than 1500 mutations are associated with HCM.Most of the studies on the pathogenicity genes of HCM in China are limited to several genes that encode muscle sections, which will inevitably lead to a decrease in the detection rate of pathogenic genes, which makes some HCM cases carrying other pathogenic genes fail to screen out the pathogenic genes.Screening and genetic research for members of their families are also out of the question.Objective to complete the sequencing of 44 genes in human cardiomyopathy related target genomes using a new generation of high-throughput sequencing technique (NGS), and to analyze the characteristics of gene mutation and the relationship between genotype and clinical phenotype.Methods Fifteen patients with familial hypertrophic cardiomyopathy (FHCM) who were admitted to Henan chest Hospital from 2012 to 2016 were enrolled. Clinical data (including medical history, physical examination, echocardiography, electrocardiogram) were collected and 44 pancardiomyopathy target genes were screened.Sanger sequencing was used to detect the specific genes of other members of the family.The pathogenicity of the newly discovered mutant gene was determined by the homology of Poly Phen-HCM and the protein sequence of different species, and compared with that of the healthy control group. Finally, the relationship between genotype and clinical phenotype of the mutant carriers was analyzed.Results among the 15 probands of hypertrophic cardiomyopathy, 9 mutations of 5 pathogenetic genes related to HCM were found in 8 probands, of which 1 case was a double gene mutation and 2 cases were newly discovered mutations, which have not been reported at home and abroad.Conclusion c.903del G mutation in exon 9 of 1.MYBPC3 gene and c.2834GA mutation in exon 26 of MYBPC3 gene have not been reported at home and abroad. It is a new pathogenicity mutation. C.903del G mutation of MYBPC3 gene has serious clinical phenotype and is prone to malignant heart rate disorder.The clinical phenotype diversity of c.2834GA mutation in exon 26 of MYBPC3 gene needs to be more active.On the basis of genetic inheritance at home, AB _ o mutation can occur. Double mutation carriers have early onset, heavy myocardial hypertrophy, severe clinical manifestations and poor prognosis.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R542.2

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本文編號：1747418