Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Objective:To analyse the pathogenicity of a family with Fabry disease and to characterise its clinical phenotype and genetic variants.Methods:A proband with Fabry disease admitted to Beijing Anzhen Hospital, Capital Medical University in December 2021 was enrolled. Clinical data, including medical history, biochemical parameters, echocardiography, and electrocardiogram, were collected from the proband and family members. The proband and his daughter underwent α-galactosidase A (α-Gal A) enzyme activity assay and Sanger sequencing of the GLA gene. Candidate variants were analyzed and classified according to the American College of Medical Genetics and Genomics guidelines.Results:The male proband (69 years old) presented with chronic renal insufficiency, electrocardiogram findings of ST-T changes, bundle branch block, and left ventricular high voltage, and echocardiographic evidence of left ventricular hypertrophy. His α-Gal A activity was markedly reduced, and genetic testing identified a hemizygous GLA c.511G>C (p.Gly171Arg) variant on the X chromosome. The proband′s asymptomatic daughter also exhibited significantly decreased α-Gal A activity and carried the heterozygous GLA c.511G>C (p.Gly171Arg) variant. Based on the American College of Medical Genetics and Genomics guidelines, this variant was classified as “likely pathogenic” and considered the underlying cause of Fabry disease in this family.Conclusion:The proband manifested chronic renal insufficiency and cardiac hypertrophy, with the GLA c.511G>C (p.Gly171Arg) variant identified as the likely-pathogenic cause of Fabry disease in this family.

Objective:To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS).Methods:An adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was enrolled as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X).Results:Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c. 206+ 2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the patients mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The heterozygous splice site variant c. 206+ 2T>G of the SMAD3 gene probably underlay the disease of this patient. The discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.

Objective:To analyse the pathogenicity of a family with Fabry disease and to characterise its clinical phenotype and genetic variants.Methods:A proband with Fabry disease admitted to Beijing Anzhen Hospital, Capital Medical University in December 2021 was enrolled. Clinical data, including medical history, biochemical parameters, echocardiography, and electrocardiogram, were collected from the proband and family members. The proband and his daughter underwent α-galactosidase A (α-Gal A) enzyme activity assay and Sanger sequencing of the GLA gene. Candidate variants were analyzed and classified according to the American College of Medical Genetics and Genomics guidelines.Results:The male proband (69 years old) presented with chronic renal insufficiency, electrocardiogram findings of ST-T changes, bundle branch block, and left ventricular high voltage, and echocardiographic evidence of left ventricular hypertrophy. His α-Gal A activity was markedly reduced, and genetic testing identified a hemizygous GLA c.511G>C (p.Gly171Arg) variant on the X chromosome. The proband′s asymptomatic daughter also exhibited significantly decreased α-Gal A activity and carried the heterozygous GLA c.511G>C (p.Gly171Arg) variant. Based on the American College of Medical Genetics and Genomics guidelines, this variant was classified as “likely pathogenic” and considered the underlying cause of Fabry disease in this family.Conclusion:The proband manifested chronic renal insufficiency and cardiac hypertrophy, with the GLA c.511G>C (p.Gly171Arg) variant identified as the likely-pathogenic cause of Fabry disease in this family.

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
Humans ; Cardiomyopathy, Dilated/genetics* ; Genetic Testing ; Genetic Counseling ; Computational Biology ; Frameshift Mutation ; Mutation ; Filamins

OBJECTIVE: To explore the correlation between clinical phenotypes and pathogenic variants in two patients with familial hypercholesterolemia. METHODS: Both patients were subjected to whole exome sequencing (WES) with a focus on the analysis of genes associated with dyslipidemia. Candidate variants were verified by Sanger sequencing of the patients and their family members. RESULTS: WES revealed that the proband 1 has harbored two heterozygous variants of the LDLR gene, namely c.1360G>A (p.D454N) and c.292G>A (p.G98S), whilst proband 2 has harbored a heterozygous c.321T>G (p.C107W) variant of the LDLR gene. Based on the guidelines from the American College of Medical Genetic and Genomics (ACMG), the above variants were respectively predicted to be likely pathogenic (PM1+PM2+PP2+PP3+PP4+PP5), variant of unknown significance (PM1+PP2+PP3), and likely pathogenic (PM1+PM2+PP2+PP4+PP5). Treatment with PCSK9 inhibitor has attained a significant effect in proband 1 but no apparent effect in proband 2. CONCLUSION Variants of the LDLR gene probably underlay the familial hypercholesterolemia in the two pedigrees. The difference in the severity of the clinical phenotypes and response to PCSK9 inhibitor treatment between the two probands may be attributed to the different genotypes of the LDLR gene. Genetic testing not only can provide a basis for clinical diagnosis, but also facilitate the choice of lipid-lowering drugs.
Humans ; China ; Hyperlipoproteinemia Type II/genetics* ; Phenotype ; Receptors, LDL/genetics*

Objective To investigate the effects of percutaneous coronary intervention(PCI)on life quality and cardiac events in elderly patients with stable angina owing to chronic coronary total occlusion(CTO).Methods Patients with stable angina due to CTO hospitalized in Beijing Anzhen Hospital from January 2015 to January 2018 were consecutively recruited in this prospective study,and were randomly divided into the combined treatment group(n=44)and the control group (n=43).Patients in the combined treatment group were treated with PCI and optimal medical therapy,and those in the control group were treated with optimal medical therapy alone.Patients followed up for 6 months after treatment.Cardiac function,life quality(Seattle angina questionnaire,SAQ)and adverse cardiovascular events were compared before and after treatment.Results A total of 87 patients were involved,with a mean age of (69.5 ± 7.2) years.Basic characteristics,including age,sex ratio,previous history,left ventricular ejection fraction,coronary artery lesions and SAQ scores,were similar between the groups(P＞0.05).After a 6 month post treatment follow up,SAQ scores improved in all patients,compared with those before treatment(P＜0.05).Moreover,patients in the combined treatment group had higher SAQ scores on physical limitation(86.3 ± 11.6 vs.76.3 ± 21.3),angina stability(67.3 ±24.5 vs.57.3±21.2)and angina frequency(93.3±4.3 vs.86.4±8.3)than those in the control group (P ＜0.05).There was no significant difference in major adverse cardiovascular event rate between the groups[18.2％(8 cases) vs.16.3％(7 cases),X2 =0.055,P＞0.05].Conclusions Combined with optimal medical therapy,PCI can improve the life quality in elderly patients with stable angina due to CTO,but has no significant influence on the short-term major adverse cardiovascular event rate.

Objective To analyze the risk factors of adverse cardiac events in adults with acute myocarditis during hospitalization and provide reference for clinical diagnosis and treatment.Methods A restrospective study was conducted in 80 patients (54 males and 26 females) with acute myocarditis over 18 years old admitted to our hospital between January 2007 and December 2016.Major adverse cardiac events (MACE) were defined as death,cardiac arrest,cardiogenic shock and ventricular fibrillation.According to whether MACE occurred during hospitalization,patients were divided into two groups:the MACE group and the non-MACE group.The differences between the two groups were compared,and the risk factors were analyzed by logistic regression.Results There were 12 patients in the MACE group and 68 patients in the non-MACE group.The age of patients in the two groups was similar.Compared with the non-MACE group,the proportion of female patient in the MACE group was higher (66.7％ vs 26.5％,P=0.015),and the systolic pressure (mmHg) was lower at admission (89.75±17.63 vs 112.49±16.35,P＜0.01),and the heart rate (beats/min) was faster (106.42±24.39 vs 82.66±20.92,P=0.001);ALT and creatinine levels in the MACE group were higher (P＜0.01),while the levels of TnI,CK-MB,CK and LDH were significantly higher (P＜0.05).The LVEF value of the MACE group was significantly lower at admission (45％ vs 60％,P=0.022),and the proportion of LVEF ＜ 50％ was also higher (58.3％ vs 19.1％,P=0.008) The proportion of prolonged QRS wave (＞120 ms) was significantly higher in the MACE group (75％ vs 17.6％,P＜0.01).In the MACE group,the proportion of diuretics and vasoactive drugs (dopamine,norepinephrine,and adrenaline) was higher (66.7％ vs 25％,91.7％ vs 4.4％,66.7％ vs 0,75％ vs 0％,all P＜0.01);the proportion of glucocorticoids and immunoglobulin was higher (33.3％ vs 8.8％,P=0.038;33.3％ vs 4.4％,P=0.008),and the proportion of ventilator,CRRT,ECMO and IABP were also higher (50％vs 1.5％,33.3％ vs 0,25％ vs 0％,25％ vs 0％,all P＜0.01).Logistic regression analysis showed that the OR value of MACE in female patients during hospitalization was 5.56 (95％CI:1.49-20.71,P=0.011).The OR value of MACE in patients with reduced LVEF at admission was 5.92 (95％CI:1.62-21.67,P=0.007).The OR value of MACE in patients with prolonged QRS wave was 14.00 (95％CI:3.29-59.55,P＜0.01).Conclusions Female patients,LVEF＜50％ at admission,and prolonged QRS wave (QRS＞120 ms) are independent risk factors for MACE in adult patients with acute myocarditis during hospitalization.

Objective ST segment elevation in adult patients with acute myocarditis is rare in adult.The purpose of this study was to report the outcome of ST segment elevation in adult patients with acute myocarditis in our hospital,in order to provide reference for clinical diagnosis and treatment.Methods A retrospective analysis of Beijing Anzhen Hospital during January 2002 to December 2015 for the diagnosis of acute myocarditis were 105 cases,divided into two groups,one group of ST elevation (ST elevation group) total 57 cases,another group of non ST elevation (non ST elevation group) total 48 cases.The clinical features,laboratory examination,treatment and prognosis were compared between the two groups.The composite primary endpoint of major cardiovascular events (MACE) during hospitalization included:mortality,cardiac shock and ventricular fibrillation.Results The average onset age of patients with ST segment elevation group and non ST segment elevation group were similar [(27.7 ± 10.1) years vs.(28.7 ± 10.0) years,P =0.603].There was a significant difference between the two group in patients of heart rate [(89 ± 22) beats/min vs.(80 ± 23) beats/min,P =0.028],systolic blood pressure on admission [(105 ± 17) mmHg vs.(115 ± 17) mmHg,P =0.003],diastolic blood pressure on admission [(66 ± 11) mmHg vs.(74 ± 11) mmHg,P =0.000],and total number of acute fulminant myocarditis [20 (35.1％) vs.7 (14.6％),P =0.024)].ST segment elevation acute myocarditis patients were significantly more at risk for MACE than non ST segment elevation acute myocarditis patients during hospitalization (P =0.04).Conclusion ST segment elevation acute myocarditis has acute onset and rapid progression.The incidence of MACE during hospitalization was significantly high.Mechanical support can be ve,ry favourable.ST segment elevation acute myocarditis is associated with excellent short-term prognosis.