一例Fabry病患者α-半乳糖苷酶基因突变和酶活性分析

目的 分析1例临床诊断的15岁典型Fabry病男性患者的临床表现、α-半乳糖苷酶A(α-GalA)基因(GLA)突变位点及其活性,并对无临床表现的患者母亲进行了相应的对照分析.方法 收集该例患者的临床资料,提取患者及其母亲、1名健康对照者的外周血基因组DNA,PCR分段扩增GLA基因的7个外显子,产物纯化后克隆入T载体进行DNA测序,检测是否存在突变位点,进一步应用荧光底物法榆测α-Gala的活性.结果 基因检测证实患者GLA基凶第7号外显子发生一个错义突变,即10036-10038位的AAG缺失(10036-10038delAAG),导致其编码的第374位的赖氨酸和第375位甘氨酸突变成精氨酸,该突变位点经国内外文献检索未见报道.该患者为带有突变基因的半合子,母亲为携带突变基因的杂合子,健康对照者未发现突变.α-GalA酶活性检测结果显示,携带该突变位点GLA基因的患者,其α-GalA酶活性只有健康对照者的50%左右,患者母亲的α-GalA酶活性为健康对照者的70%左右.结论 对临床疑似的Fabry病患者及其亲属,进行GLA基冈突变检测,结合α-GalA酶活性检测,有助于早期筛选出家系中的其他患者,能更加深入地了解Fabry病的分子发病机制.     

一个Fabry病家系的GLA基因突变分析

目的对一个临床诊断的非典型Fabry病患者进行α半乳糖苷酶基因(GLA)进行突变分析.方法抽取患者家系中4名成员的外周血基因组DNA,PCR分段扩增位于Xq22的GLA基因的7个外显子,产物纯化后直接进行DNA测序检测突变.结果测序显示,男性患者GLA基因的第6外显子存在CGA301CAA(Arg301Gln)突变,该患者为带有突变基因的半合子,母亲为携带突变基因的杂合子,哥哥及父亲为CGA301野生型的半合子.结论对临床诊断的Fabry病患者及其亲属,进行GLA基因突变检测可以进行基因诊断,并有助于早期筛选出家系中的其他患者.     

一个Fabry病家系的GLA基因突变分析

目的 对一个临床诊断的非典型Fabry病患者进行α半乳糖苷酶基因(GLA)进行突变分析。方法 抽取患者家系中4名成员的外周血基因组DNA，PCR分段扩增位于Xq22的GLA基因的7个外显子，产物纯化后直接进行DNA测序检测突变。结果 测序显示，男性患者GLA基因的第6外显子存在CGA301CAA(Arg301Gln)突变，该患者为带有突变基因的半合子，母亲为携带突变基因的杂合子，哥哥及父亲为CGA301野生型的半合子。结论 对临床诊断的Fabry病患者及其亲属，进行GLA基因突变检测可以进行基因诊断，并有助于早期筛选出家系中的其他患者。     

家族性血脂异常LPL基因新突变位点分析

目的:对收集的1例血脂异常家系的致病基因进行全外显子测序,确定其突变基因位点。方法:收集在我院就诊的1例血脂异常患者及其家系成员的临床资料,采集患者及相关家系成员外周血样本并提取基因组DNA,利用目标外显子捕获技术和二代测序技术对先证者的与血脂异常有关的基因进行基因突变筛查,并使用Sanger测序法验证可疑突变位点并筛查患者家系成员和100例健康人,确定该家系患者的致病突变基因,使用Polyphen2、MutationTaster、SIFT和Provean这4种软件进行突变基因功能检测,并利用Swiss-Model软件分析突变前后的蛋白质三维结构模型。结果:在受检人样品中检测到LPL基因的纯合变异c.1322+1G>A(编码区第1322+1位核苷酸由G变为A),在其子女样品中检测到LPL基因同位点的杂合变异。4种预测软件均预测该突变为有害突变,Swiss-Model软件结果显示该突变位点导致442位的缬氨酸突变为终止密码子,可能影响蛋白质的剪切和活化功能。结论:本研究应用全外显子测序技术在一血脂异常家系中发现LPL基因新的突变位点:LPL c.1322+1G>A。该突变可能...     

肥厚型心肌病家系携带MYH7和TTN以及GLA基因突变分析

目的对收集的肥厚型心肌病(hypertrophic cardiomyopathy)家系的致病基因进行突变位点分析,阐明基因型与临床表型的关系。方法利用靶向外显子捕获测序的方法对肥厚型心肌病先证者的30个肥厚型心肌病相关的基因进行全外显子扩增和高通量测序,进一步通过Sanger测序法在该家系内及另选择200例健康志愿者进行验证,确定该家系患者的致病突变。对肥厚型心肌病的家系调查资料包括临床表现、体格检查、心电图及超声心动图或心脏核磁共振检测结果。结果该家系12例有血缘关系的研究对象中4例携带MYH7基因c.G2389A杂合突变(A797L)。4例携带TTN基因c.G10306T杂合无义变异(E3436X)。3例携带GLA基因c.G196C杂合突变,该突变位点位于GLA基因的第2号外显子并使66位的谷氨酸变为谷氨酰胺。该家系先证者同时携带上述3种突变基因,先证者肥厚型心肌病发病早,临床症状重,彩色超声显示室间隔梭形肥厚(厚度为24mm),心肌回声斑点状增强,心肌纹理排列紊乱,运动减弱,心脏核磁共振显示室间隔及毗邻前壁增厚,延迟强化室间隔心肌壁内可见轻度晕状强化。结论 MYH7基因c.G2389A突变可能是肥厚型心肌病的致病突变,携带复合突变的家系成员心肌病发病早、表型重。     

一家族性高胆固醇血症家系低密度脂蛋白受体基因突变分析

为分析一家族性高胆固醇血症家系低密度脂蛋白受体的基因突变，提取患儿及其父母外周血基因组DNA，用聚合酶链反应扩增低密度脂蛋白受体基因的18个外显子。用单链构象多态性分析检测聚合酶链反应产物，对单链构象多态性分析电泳结果异常者进行DNA序列分析。结果发现，单链构象多态性分析发现患者及其母亲第10外显子存在一异常条带。DNA测序结果证实患者第10外显子的471位密码子由AGA同义突变为AGG，483住密码子由TGG突变为TAG，导致在483住提前出现终止密码子。本研究利用聚合酶链反应一单链构象多态性分析方法报道了一个新的低密度脂蛋白受体突变位点。     

汉族肥厚型心肌病患者中Fabry病的基因突变鉴定和家系研究

目的探讨基因检测在汉族肥厚型心肌病(hypertrophic cardiomyopathy,HCM)患者中Fabry病的基因突变情况及家系筛查中的应用,并分析基因型与表型的关系。方法应用半导体靶向二代测序平台筛查在阜外医院诊断为HCM的217例患者,应用Sanger测序验证先证者和家系内成员的GLA基因突变位点,收集GLA突变携带者的临床资料并进行基因型与表型关联分析。结果发现2例男性Fabry病先证者(在HCM中占比0.93%)。1例携带GLA基因错义突变c.887TC(p.M296T),表现为迟发心脏型Fabry病;对其一家四代中的25个家庭成员进行家系突变筛查,结果发现有4个女性杂合突变携带者,其中1个确诊为HCM。另1例携带GLA基因错义突变c.758TC(p.I253T),表现为经典型Fabry病,累及肾和神经系统。对其一家四代中的32个家系成员进行家系调查,发现2个女性杂合突变携带者和2个男性早发心脏性猝死。两例先证者经室间隔心肌切除术后梗阻解除,后者应用分子伴侣药物Migalastat治疗后肾功能稳定于31 ml/min。结论首次发现Fabry病在汉族HCM中并不少见,基因检测有助于早期鉴别诊断及筛查家系内突变携带者。GLA c.758TC为恶性基因型,男性突变携带者猝死风险高危,室间隔心肌切除术和Migalastat有助于改善预后。     

镫骨强直伴拇指（趾）宽大综合征家系NOG基因新发突变鉴定及临床特征分析

［摘要］　目的　分析一个罕见的镫骨强直伴拇指（趾）宽大综合征(SABTT)家系（编号HuB-341）的临床及遗传学特征,应用新一代高通量测序鉴定其致病基因。方法　对该家系成员进行病史调查、体格检查、影像学检查以及听力学检查,绘制家系图谱。同时抽取家系成员外周静脉血并提取DNA,对先证者进行全外显子组测序,对候选基因通过Sanger测序进行家系验证,明确该家系的致病基因。结果　HuB-341家系来自湖北省武汉市,2代3人。先证者为家系唯一耳聋患者,临床表现为双耳传导性聋并伴有特征性面容、拇趾宽大、弱视及远视。对先证者进行全外显子组测序鉴定了NOG基因一个新的突变位点,即c.679G>T,引起编码第227位的谷氨酸突变为终止密码子（p.Glu227Ter）。家系验证提示该突变为新生突变。该突变在多物种间是保守的。结论　该家系临床诊断为SABTT,通过先证者全外显子组测序及家系验证,鉴定了NOG基因一个新的突变位点,即c.679G>T（p.Glu227Ter）。该突变为家系的致病突变,临床诊断和分子诊断相结合提高了对该罕见病的认识,为该家系的遗传咨询提供了科学依据。     

一个新的肝细胞核因子1α仪基因突变致青少年的成人起病型糖尿病3型家系报道

目的探讨一个青少年的成人起病型糖尿病（MODY）家系的致病基因。方法对一例发病9年的32岁女性糖尿病患者家系成员进行调查,该家系中有两代糖尿病患者,采用目标区域捕获高深度测序技术在先证者中找到突变基因,使用Sanger测序技术验证突变位点并筛查其他家系成员。结果基因检测发现家系中3个个体携带肝细胞核因子1仅（HNF·1α）基因V380Cfs。39移码突变,该突变在家系中表现为与糖尿病共分离。结论该家系为一个新的HNF-1α仅基因突变所致MODY3家系。     

一个Ⅱa型多内分泌腺瘤病家系的RET原癌基因突变研究

目的 检测一个Ⅱa型多内分泌腺瘤（MEN-Ⅱa)病家系中RET原癌基因的突变情况。方法 提取9名家系成员外周血基因组DNA，对RET原癌基因第10和第11外显子进行聚合酶链反应（PCR），PCR产物进行直接DNA测序。结果 家系中2例经病理确诊的患者存在RET原癌基因第11外显子Cys(TGC)634Gly(GGC)错义突变，另筛查出4名成员为该突变基因携带者，其中2例经B超检查发现甲状腺有新生物，1例双侧甲状腺及双侧肾上腺有新生物。1例15岁的突变基因携带者无临床表现。结论 对MEN-Ⅱa家系的基因分析证实RET原癌基因第11外显子在密码子634存在TGC→GGC突变，对MEN-Ⅱa能在基因水平作出诊断，对MEN-Ⅱa家系成员作分子遗传学分析有助于判断患MEN-Ⅱa的危险性和临床上作进一步处理。     

MYBPC3基因p.Ile852Val突变与家族性肥厚型心肌病的相关性研究

目的:MYBPC3基因突变是肥厚性心肌病(HCM)的常见原因,本研究对导致HCM的一种新型的MYBPC3基因突变进行研究。方法:纳入了1例HCM患者及其家系中的8个亲属,同时纳入13名健康志愿者作为对照。对HCM患者家系及对照组成员进行基因测序,同时对HCM患者家系进行谱系分析、临床评估和基因分型。结果:在患者家系中,患者母亲及外祖父为肥厚型心肌病患者,基因测序发现患者及该2名亲属均存在MYBPC3基因p.Ile852Val杂合突变,其余5名亲属及健康对照组均无此突变。患者及其母亲临床症状相对较轻,但表现并不相同,外祖父长期卧床,症状较重,有严重胸闷气喘,在研究过程中猝死。结论:MYBPC3基因p.Ile852Val杂合突变与肥厚型心肌病相关,该突变为一种新型的导致HCM的基因突变,且携带该突变的HCM患者临床症状存在一定差异性。     

Transthyretin amyloidosis: a phenocopy of hypertrophic cardiomyopathy

Objectives: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder that affects over one in 500 persons worldwide. The autosomal dominant transmission of HCM implies that many relatives are at risk for HCM associated morbidity and mortality, therefore genetic testing and counselling is of great importance. However, in only 50–60% of the patients a mutation is found, which hampers predictive genetic testing in relatives. In HCM patients in whom the causal mutation has not been identified (yet), phenocopies of HCM – i.e. diseases that mimic HCM – could be responsible for the HCM phenotype. One of the HCM phenocopies is transthyretin amyloidosis (ATTR), caused by mutations in the transthyretin (TTR) gene.

Methods: From 697 HCM index patients referred to our cardiogenetics outpatient clinic and tested for HCM associated genes between January 1997 and December 2012, we selected the ones without a detected causal mutation (n?=?345). In these patients, additional DNA analysis of the TTR gene was performed.

Results: In four patients (1.2%), a TTR mutation was detected (E7G, V30M, T119M, V122I). The E7G mutation is probably a non-pathogenic mutation. The T119M mutation is a known TTR mutation, but does not cause a cardiac phenotype. So in two (0.6%) patients, TTR analysis identified the cause of their HCM.

Conclusions: ATTR should always be considered in patients with unexplained HCM, especially because of the great benefit of an early diagnosis regarding treatment and prognosis.     

Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure

OBJECTIVE: To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with beta myosin heavy chain (beta MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. DESIGN: Molecular analysis of beta MHC and mtDNA gene defects in patients with HCM. SETTING: Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. PATIENTS: Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional affected patients and 27 unaffected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy. INTERVENTION: Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. MAIN OUTCOME MEASURES: Screening for mutations in beta MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. RESULTS: One proband (kindred A) (plus seven affected relatives) had arginine 249 glutamine (Arg249Gln) beta MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel beta MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)-->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but different from those of the two patients with Lys450Glu plus T9957C(Phe-->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaffected in the two in kindred C. CONCLUSIONS: beta MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although beta MHC gene mutations seem to be the true determinants of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in beta MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.     

MYBPC3基因G12101A和MYH7基因G15391A突变与肥厚型心肌病临床表型

目的 研究中国人家族性肥厚型心肌病(HCM)的致病基因突变位点,分析基因型与临床表型的相互关系.方法 在2个中国汉族HCM家系中进行心脏肌钙蛋白T基因(TNNT2)、心脏肌球蛋白结合蛋白C基因(MYBPC3)和心脏β-肌球蛋白重链基因(MYH7)的突变筛查,聚合酶链式反应(PCR)扩增基因功能区外显子片段并对PCR产物进行测序分析.结果 在ZZJ家系接受调查的8名成员中有4名成员携带MYBPC3基因G12101A杂合突变,该突变位点位于MYBPC3基因的21号外显子并使668位的精氨酸(R)转换为组氨酸(H),携带该突变的家族成员发病年龄较晚且均无梗阻及晕厥史.在FHL家系接受调查的6名成员中有3名成员携带MYH7基因G15391A杂合突变,该突变位点位于MYH7基因的23号外显子并使930位的谷氨酸(E)转换为赖氨酸(K),该突变导致的临床表型呈现发病年龄早、梗阻率高以及外显率高的特点.两家系成员TNNT2基因未发现突变,且正常对照组相同位置未发现异常.结论 MYBPC3基凶和MYH7基因是我国家族性HCM的致病基因,MYBPC3基因G12101A突变所致HCM临床症状相对较轻,而MYH7基因G15391A突变所致HCM临床症状出现早、进展较快且预后较差,是一种恶性突变.     

Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects.

AIMS: The E101K mutation in the alpha-cardiac actin gene (ACTC) has been associated with apical hypertrophic cardiomyopathy (HCM). As prominent trabeculations were described in some carriers, we screened for the E101K mutation in our index patients with HCM, dilated cardiomyopathy (DCM), or left ventricular non-compaction (LVNC). METHODS AND RESULTS: Clinical, echocardiographic, and genetic screening by restriction fragment length polymorphism of the ACTC E101K mutation in 247 families with HCM, DCM, or LVNC. The mutation was found in five index patients (one with LVNC and four with HCM). Clinical and morphological data were obtained from 94 family members. Forty-six individuals had cardiomyopathy (43 with the mutation and three with no genetic study): 23 fulfilled criteria for LVNC, 22 were diagnosed as apical HCM, and one had been diagnosed as restrictive cardiomyopathy. There had been one heart transplant and one congestive heart failure death in patients with severe diastolic dysfunction, and five premature sudden deaths. The E101K mutation was not found in 48 unaffected relatives. Septal defects (eight atrial and one ventricular) were found in nine mutant carriers from four families, and were absent in relatives without the mutation (P = 0.003). CONCLUSION: LVNC and HCM may appear as overlapping entities. The ACTC E101K mutation should be considered in the genetic diagnosis of LVNC, apical HCM, and septal defects.     

A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy

OBJECTIVES: The purpose of this study was to understand the clinical and molecular features of familial hypertrophic cardiomyopathy (HCM) in which a mitochondrial abnormality was strongly suspected. BACKGROUND: Defects of the mitochondrial genome are responsible for a heterogeneous group of clinical disorders, including cardiomyopathy. The majority of pathogenic mutations are heteroplasmic, with mutated and wild-type mitochondrial deoxyribonucleic acid (mtDNA) coexisting within the same cell. Homoplasmic mutations (present in every copy of the genome within the cell) present a difficult challenge in terms of diagnosis and assigning pathogenicity, as human mtDNA is highly polymorphic. METHODS: A detailed clinical, histochemical, biochemical, and molecular genetic analysis was performed on two families with HCM to investigate the underlying mitochondrial defect. RESULTS: Cardiac tissue from an affected child in the presenting family exhibited severe deficiencies of mitochondrial respiratory chain enzymes, whereas histochemical and biochemical studies of the skeletal muscle were normal. Mitochondrial DNA sequencing revealed an A4300G transition in the mitochondrial transfer ribonucleic acid (tRNA)(Ile) gene, which was shown to be homoplasmic by polymerase chain reaction/restriction fragment length polymorphism analysis in all samples from affected individuals and other maternal relatives. In a second family, previously reported as heteroplasmic for this base substitution, the mutation has subsequently been shown to be homoplasmic. The pathogenic role for this mutation was confirmed by high-resolution Northern blot analysis of heart tissue from both families, revealing very low steady-state levels of the mature mitochondrial tRNA(Ile). CONCLUSIONS: This report documents, for the first time, that a homoplasmic mitochondrial tRNA mutation may cause maternally inherited HCM. It highlights the significant contribution that homoplasmic mitochondrial tRNA substitutions may play in the development of cardiac disease. A restriction of the biochemical defect to the affected tissue has important implications for the screening of patients with cardiomyopathy for mitochondrial disease.     

心脏型肌球蛋白结合蛋白C基因IVS15-1G＞A突变导致肥厚型心肌病

目的研究中国人肥厚型心肌病（HCM）致病基因,分析基因型与临床表型的关系。方法在一HCM家系中进行心脏型肌球蛋白结合蛋白C基因（MYBPC3）和β-肌球蛋白重链基因（MYH7）突变筛查,利用聚合酶链反应（PCR）扩增其功能区的外显子片段,双脱氧末段终止法测序。家系调查资料包括临床表现、体格检查、心脏超声和心电图。结果在该家系8例有血缘关系的研究对象中6例携带MYBPC3（gi：Y10129）G8887A突变,正常对照同一位置未见异常。该突变位点是MYBPC3基因15内含子的剪接位点的受体位点（IVS15-1G〉A）,其中3例携带者发病,表现为轻微的胸闷、胸痛和不对称性室间隔轻度肥厚（13～14mm）,发病较晚（48～75岁）。MYH7基因未发现突变。结论MYBPC3基因IVS15—1G〉A突变是该HCM家系的致病突变,其携带者临床表型较好。对于症状轻微、发病较晚的HCM患者,首选MYBPC3基因进行突变筛查是较为合理可行的方法。     

心脏型肌球蛋白结合蛋白C基因13261 G＞A突变导致肥厚型心肌病的临床表型分析

目的研究中国人肥厚型心肌病致病基因,分析基因型与临床表型的关系。方法在一肥厚型心肌病家系中进行心脏型肌球蛋白结合蛋白C基因（MYBPC3）和β-肌球蛋白重链基因（MYH7）突变筛查,利用聚合酶链反应（PCR）扩增其功能区的外显子片段,双脱氧末段终止法测序。家系调查资料包括临床表现、体格检查、心脏超声和心电图。结果在该家系27例有血缘关系的研究对象中9例携带MYBPC3 13261 G〉A（G758D）突变,正常对照组同一位置未见异常。该突变位点是MYBPC3基因第23号外显子的甘氨酸突变为天冬氨酸,其中2例携带者发病,一例表现为心室扩大,左室射血分数减低等扩张型心肌病样表现,伴室间隔不对称肥厚,厚度为14mm,另外一例患者为典型的肥厚型心肌病表现。MYH7基因未发现突变。结论MYBPC3基因13261 G〉A突变是该肥厚型心肌病家系的致病突变,其外显率为22％,其中一例患者表现为肥厚型心肌病的扩张相,MYBPC3基因G758D突变可能是肥厚型心肌病进展为扩张型心肌病样改变的原因之一。对临床表现为扩张型心肌病的患者进行家族史调查及基因检查十分必要。     

散发性肥厚型心肌病β肌球蛋白重链及肌钙蛋白T基因突变的研究

目的研究β肌球蛋白重链(MYH7)及肌钙蛋白T(TNNT2)突变是否为散发性肥厚型心肌病(SHCM)患者的致病基因。方法对50例无血缘关系家族中仅1例患病且无一级亲属猝死史的SHCM患者及80例有一级亲属的SHCM患者进行MYH7及TNNT2扫描。提取所有DNA片段用PCR扩增后以双脱氧末端终止法测序。结果(1)50例SHCM患者中均未发现TNNT2基因突变。有1例MYH7突变,位于20号外显子上的T13659C突变(Ile736Thr);(2)80例家族成员中未发现MYH7及TNNT2基因突变。结论SHCM患者MYH7及TNNT2基因突变发生率低,可能不是SHCM的主要致病基因。     

相同基因型而不同表现型的PRKAG2基因突变一家系报道

目的 位于7号染色体上的腺苷一磷酸激活的蛋白激酶γ^2调节亚单位基因（PRKAG2基因）调节代谢通路。报道一个具有PRKAG2基因突变而临床表现型不同的家系。方法 使用DNA直接测序法,对一个具有多种形式心律失常的患者家系（13例患者）进行PRKAG2外显子及外显子和内含子拼接部位序列筛查寻找基因突变。结果 心电图显示患者家系存在窦性心动过缓、短PR间期、完全性右束支传导阻滞、房室传导阻滞和房性心动过速。其中3例患者在年轻时发生猝死,没有1例有预激综合征（预激）表现,只有1例有心肌肥厚。DNA测序结果显示,该家系所有患者皆有一个PRKAG2错义突变（R302Q）。这个基因突变以前曾描述并与预激和左室肥厚有关。结论 PRKAG2基因突变不仅导致预激而且与多种临床表现型有关。完全性右束支传导阻滞、窦性心动过缓、短PR间期应该高度怀疑有PRKAG2基因突变的可能。