Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC) Methods Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two dimensional echocardiography (2 DE) and a signal averaging electrocardiogram Programmed ventricular stimulation was performed in five patients Results All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2 DE Fourteen persons had abnormal findings indicating ARVC Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall Twenty five persons (seven patients and 18 family members) had abnormal findings in ECG Positive ventricular late potential was recorded in 13 persons (six patients) Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS) Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle Two members of one family died suddenly One member was a dwarf with ARVC Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients) Conclusion Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle

Alpha-1 Antitrypsin Deficiency Family Study

According to the latest World Health Organization report 64 million people suffer from Chronic Obstructive Pulmonary Disease （COPD）, 3 million people died from COPD and it is predicted that COPD will become the third leading cause of death worldwide by 2030. The alpha-1 antitrypsin deficiency is a rarely diagnosed hereditary disease caused by a genetic mutation and it is one of the most prevalent genetic disorders primarily affecting the lungs, especially in the form of COPD or emphysema, but in some cases also the liver or skin. The Global Initiative for Chronic Obstructive Lung Disease recommends all patients with COPD at a young age or significant family history to be examined for alpha-1 antitrypsin deficiency. This article presents the case of a 42 year old, female patient, Portuguese, with history of Chronic Obstructive Pulmonary Disease, 40 pack units/year smoker, with unknown family history, coming to her family doctor with breath shortness, especially during physical activities, with unsatisfying response to pharmacological prescribed therapy. Physical examination was normal. Alpha- 1 antitrypsin deficiency was confirmed by blood testing. All patient＇s first degree relatives were investigated showing low alpha-1 antitrypsin blood concentrations thus genetic tests were later performed. This case reinforces the need for primary care physicians to be aware of alphal-antitrypsin deficit as an underdiagnosed clinical entity.

Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles

AIM: To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC).

An algorithm for family screening for coeliac disease

AIM: To assess the level of undiagnosed coeliac disease (CD) in relatives of patients affected by the condition. METHODS: We collected blood from 914 relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG antibodies, confirming any positive IgA tTG results with an IgA EMA and looked for evidence of IgA deficiency in those who were IgG tTG positive alone, and performed IgG1 EMA in these individuals. We undertook HLA typing where positive screening was found, and this confirmed a strong prevalence of HLA- DQ2 in the coeliac population. Follow-up small intestinal biopsy was undertaken in cases with positive serological screening, wherever possible. RESULTS:Use of this serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6% of first degree relatives of probands. CONCLUSION:Our data suggests that first degree relatives of individuals with CD should be screened for this condition.

Family and twin studies in inflammatory bowel disease

Studies examining the inheritance of inflammatory bowel disease （IBD） within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn＇s disease （CD） is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis （UC） and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.

Nitric Oxide:from a mysterious labile factor to the molecule of the Nobel Prize Recent progress in nitric oxide research

NO is now known to be an important messenger molecule in biology.It regulates a variety of functions within cells and tissues including vasodilation, neurotransmission and immunological process. This review will focus on the nitric oxide synthase gene family and recent progress on molecular genetic analysis of NOS1, NOS2 and N0S3 genes.

Relationship Between Polymorphism of Cystathionine beta Synthase Gene and Congenital Heart Disease in Chinese Nuclear Families

Objective To study the relationship between polymorphism of cystathionine beta synthase （CBS） gene and development of congenital heart disease （CHD）. Methods One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method, Results The frequencies of three genotypes （w/w, w/m, and m/m） in control group were 27.2%, 58,4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67,9% in patients and 55.7% in controls CHD parents＇ genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families. Conclusions CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.

Studies on the History of Pangda Family in Markham

The famous female writer Ma Lihua in her well- known book The Red Mountain Ranges in East Tibet described the social status and influence of the Pangda family.She wrote:"The famous Pangda family in Tibetan pre-modern society stands on both

Arrhythmogenic cardiomyopathy with left ventricular involvement versus ischemic heart disease: lessons learned from the family study and the reviewed autopsy of a young male

Ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD) and often non-thrombosed severe coronary stenoses with or without myocardial scars are detected.Left dominant arrhythmogenic cardiomyopathy (LDAC) is a life-threating rare disease which has been more thoroughly studied in the last 10years.The macroscopic study of an SCD victim was conducted and re-evaluated 9years later.The cardiological work-up in his firstdegree relatives initially comprised an electrocardiogram (ECG) and an echocardiogram.When they were re-evaluted 9years later,a cardiac magnetic resonance,an ECG-monitoring,an exercise testing and a genetic study were performed and the pedigree was extended accordingly.In 2008,an IHD was suspected in the sports-triggered SCD of a 37-year-old man upon the postmortem (75% stenosis of the left main and circumflex coronary arteries;the subepicardial left ventricular fibrofatty infiltration with mild myocardial degeneration was assumed to be a past myocardial infarction).No cardiomyopathy was identified in any of the two proband's sisters.Nine years thereafter,distant relatives were diagnosed with LDAC due to a pathogenic desmoplakin mutation.The reanalysis of the two sisters showed ventricular arrhythmias in one of them without structural heart involvement and the reviewed postmortem of the proband was reclassified as LDAC based on the fibrofatty infiltration;both were mutation carriers.The completion of the family study on 19 family members yielded one SCD due to LDAC (the proband),three living patients diagnosed with LDAC (two with a defibrillator),one mutation carrier without structural ventricular involvement,and 14 healthy relatives (who were discharged) with a very good co-segregation of the mutation.Although rare,LDAC exists and sometimes its differential diagnosis with iHD has to be faced.Modifying previous postmortem misdiagnoses can help family screening to further prevent SCDs.

Does Population Aging Hinder the Accumulation of Human Capital?Evidence from China

There is no consensus on the impact of population aging on education investment.To explore this question,we first build an overlapping generations(OLG)model to theoretically analyze the effect of population aging on human capital investment in China,and then test our theory by conducting an empirical study based on micro household data.We find the following.(1)Theoretically,the OLG model shows that population aging has a crowding-out effect on education investment.(2)Empirically,the results show that the share of education and training expenditures decreases by 5.27 percentage points as the ratio of old people in the household increases by 100 percentage points,which confirms the crowding-out effect of population aging on human capital investment.(3)The crowding-out effect is far more intense on urban households than on rural households since health care expenditures will be greater in urban areas as population aging increases.(4)A quantile regression indicates that the negative effect of population aging on the share of educational expenditure is concentrated in households with higher shares of education expenditures.We confirm the robustness of our results using regional fixed effect and instrumental variable(Ⅳ)regressions.

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background:Family studies support a genetic predisposition to inflammatory bowel diseases(IBD),but known genetic variants only partially explain the disease heritability.Families withmultiple affected individuals potentially harbour rare and highimpact causal variants.Long regions of homozygosity due to recent inbreedingmay increase the risk of individuals bearing homozygous loss-of-function variants.This study aimed to identify rare and homozygous genetic variants contributing to IBD.Methods:Four families with known consanguinity and multiple cases of IBD were recruited.In a family-specific analysis,we utilised homozygosity mapping complemented by whole-exome sequencing.Results:We detected a single region of homozygosity shared by Crohn’s disease cases from a family of Druze ancestry,spanning 2.6Mb containing the NOD2 gene.Whole-exome sequencing did not identify any potentially damaging variants within the region,suggesting that non-coding variation may be involved.In addition,affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1,WHAMM,DENND3,and C5.Conclusion:This study examined the potential contribution of rare,high-impact homozygous variants in consanguineous families with IBD.While the analysis was not designed to achieve statistical significance,our findings highlight genes or loci that warrant further research.Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn’s disease.