CAJ | 학술논문

β肌球蛋白重链基因 Pro731 Ser 突变与家族性肥厚型心肌病的相关性研究
β기구단백중련기인 Pro731 Ser 돌변여가족성비후형심기병적상관성연구
Pro731Ser mutation in the β-myosin heavy chain and hypertrophic cardiomyopathy in a Chinese pedigree

万方数据

中华心血管病杂志中華心血管病雜誌 중화심혈관병잡지
Chinese Journal of Cardiology
2014年 7期 571-576 ,共6页

赵新涛%吴亚杰%陈伊%冯新星%宋莹%王怡璐%邹玉宝%王继征%邵一兵%惠汝太%宋雷%王旭

조신도%오아걸%진이%풍신성%송형%왕이로%추옥보%왕계정%소일병%혜여태%송뢰%왕욱

心肌病,肥厚性%肌球蛋白重链%基因型%表型心肌病,肥厚性%肌毬蛋白重鏈%基因型%錶型
심기병,비후성%기구단백중련%기인형%표형
Cardiomyopathy,hypertrophic%Myosin heavy chains%Genotype%Phenotype

目的：研究中国汉族人群家族性肥厚型心肌病的致病基因突变，分析基因型与表型的联系。方法研究病例资料收集于2009年阜外心血管病医院门诊。利用高通量测序对1个中国汉族肥厚型心肌病家系的26个致病基因进行筛查，发现的变异通过Sanger测序验证。在家系成员中筛查发现的致病突变，对突变携带者的表型进行分析。结果包括先证者在内13例携带MYH7基因Pro731Ser错义突变，疾病与突变共分离。其他家系成员和307名正常对照未发现此突变。携带者中10例为肥厚型心肌病患者，3例为无症状携带者，患者中有8例伴有呼吸困难、心悸、胸痛、黑矇、晕厥等症状，先证者已出现严重的心力衰竭，5例患者发病年龄小于16岁，家系中至少有1人猝死。结论MYH7基因Pro731Ser错义突变为肥厚型心肌病的致病基因突变，能够产生恶性的临床表现，但也呈现明显的临床异质性。
목적：연구중국한족인군가족성비후형심기병적치병기인돌변，분석기인형여표형적련계。방법연구병례자료수집우2009년부외심혈관병의원문진。이용고통량측서대1개중국한족비후형심기병가계적26개치병기인진행사사，발현적변이통과Sanger측서험증。재가계성원중사사발현적치병돌변，대돌변휴대자적표형진행분석。결과포괄선증자재내13례휴대MYH7기인Pro731Ser착의돌변，질병여돌변공분리。기타가계성원화307명정상대조미발현차돌변。휴대자중10례위비후형심기병환자，3례위무증상휴대자，환자중유8례반유호흡곤난、심계、흉통、흑몽、훈궐등증상，선증자이출현엄중적심력쇠갈，5례환자발병년령소우16세，가계중지소유1인졸사。결론MYH7기인Pro731Ser착의돌변위비후형심기병적치병기인돌변，능구산생악성적림상표현，단야정현명현적림상이질성。
Objective To identify the casual mutation of a Chinese pedigree with hypertrophic cardiomyopathy (HCM),and to analyze the genotype-phenotype relationship.Methods The coding exons of 26 reported disease genes were sequenced by targeted resequencing in the proband and the identified mutation were detected with bi-directional Sanger sequencing in all family members and 307 healthy controls.The genotype-phenotype correlation was analyzed in the family.Results A missense mutation (c.2191C>T, p.Pro731Ser) in the 20th exon of MYH7 gene was identified.This mutation was absent in 307 healthy controls and predicted to be pathogenic by PolyPhen-HCM.Totally 13 family members carried this mutation , including 10 patients with HCM and 3 asymptomatic mutation carriers.The proband manifested severe congestive heart failure and 8 patients expressed various clinical manifestations of heart failure , including dyspnea , palpitations , chest pain , amaurosis or syncope.Five patients were diagnosed as HCM at the age of 16 or younger.One family member suffered sudden cardiac death.Conclusions The Pro731Ser of MYH7 gene mutation is a causal and malignant mutation linked with familiar HCM.