十个汉族家族性肥厚型心肌病MYH7、MYBPC3和TNNT2基因筛查结果及相应的临床特征  

Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype

作　　者：刘文玲[1] 谢文丽[2] 胡大一[1] 朱天刚[1] 李运田[3] 孙艺红[1] 李翠兰[1] 李蕾[1] 李田昌[4] 边红[4] 仝其广[4] 杨松娜[1] 范瑞云 崔炜[6] 

机构地区：[1]北京大学人民医院心内科,100044 [2]北京电力医院心内科 [3]解放军三○五医院心内科 [4]首都医科大学附属同仁医院心脏中心 [5]解放军二六六医院心内科 [6]河北医科大学二院心内科

出　　处：《中华心血管病杂志》2006年第3期202-207,共6页Chinese Journal of Cardiology

摘　　要：目的研究10个汉族家族性肥厚型心肌病的致病基因及突变特点,分析基因型与临床表型的相互关系。方法对10个无血缘关系的汉族家族性肥厚型心肌病的家系的MYH7基因、MYBPC3基因和TNNT2基因进行扫描,聚合酶链式反应扩增其外显子及剪接部位基因组DNA片段,直接测序分析,并分析各突变患者相应临床表型特点。结果10个汉族家族性肥厚型心肌病的家系中5个家系发现上述基因突变,3个家系MYH7基因发生错义突变,分别为Arg663His、Glu924Lys和Ile736Thr,Glu924Lys在中国患者中首次发现。这3个家系中3例患者猝死;2个家系MYBPC3基因发生错义突变、剪接突变和移码突变,1个家系先证者为复合突变即18外显子错义突变Arg502Trp及27外显子剪接突变即IVS27+12C>T,先证者之母携带错义突变,先证者之父携带剪接突变;在另一家系首次发现Gly347fs移码突变,该家系中1例猝死。10个家系中未发现TNNT2基因的功能区突变,但在内含子3中发现一个STR多态性即CTTCT5个碱基的插入/缺失,7个家系先证者发现D基因型。结论MYH7基因为中国汉族家族性肥厚型心肌病最常见致病基因,临床表现较重,猝死率较高。MYBPC3突变也较常见,症状较轻,发病较晚,但复合突变发病早、症状重。同一突变的临床表型存在异质性提示多因素参与了肥厚型心肌病的发生与发展。Objective The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy （HCM）. Methods There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients （ 14 male） aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene （ MYH7 ）, cardiac myosin-binding protein C （ MYBPC3 ） and cardiac tropenin T gene （TNNT2） were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype. Results Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 （Arg663His, Glu924Lys and Ile736Thr） were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20---48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation （ArgS02Trp and splicing mutation IVS27 ＋ 12C 〉T） and 1 with novel frame shift mutation （Gly347fs） and the latter pedigree has sudden death history. No mutation was identified in TNNT2. Conclusions Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.

关 键 词：心肌病 肥大性 家族性? 基因 突变 表型 

分 类 号：R542.2[医药卫生—心血管疾病] R394[医药卫生—内科学]