Profile of plasma microRNAs as a potential biomarker of Wilson's disease.

Background: Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs.

Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria.

The p.(Tyr400_Phe402del) mutation in the LDL receptor () gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences.

NOS3 rs1799983 and rs2070744 polymorphisms and their association with advanced chronic kidney disease and coronary heart disease in Canarian population with type 2 diabetes.

Context: Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease.

Objective: To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island.

Design: Cross-sectional case-control study.

A Common Variant at the 3'untranslated Region of the CCL7 Gene (rs17735770) Is Associated With Decreased Susceptibility to Coronary Heart Disease.

Monocytes participate in the development of atherosclerosis through the action of cytokines and other inflammatory mediators. Among them, CCR2 and its ligands, CCL2 and CCL7 play an important role, so the main objective of this work was to determine whether genetic variants affecting their activity were associated with cardiovascular disease. A cohort of 519 patients that have suffered coronary events was analyzed under a propensity score-matching protocol selecting a homogeneous set of cases and controls, according to age, sex, smoking status, dyslipidemia, arterial hypertension and type 2 diabetes as risk factors.

EHF is a novel regulator of cellular redox metabolism and predicts patient prognosis in HNSCC.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous disease with relatively high morbidity and mortality rates. The lack of effective therapies, high recurrence rates and drug resistance driven in part, by tumor heterogeneity, contribute to the poor prognosis for patients diagnosed with this cancer. This problem is further exacerbated by the fact that key regulatory factors contributing to the disease diversity remains largely elusive.

Clinical and Pharmacological Parameters Determine Relapse During Clopidogrel Treatment of Acute Coronary Syndrome.

The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs. A total of 477 patients receiving double antiaggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 year to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, ST-segment-elevation myocardial infarction, or non-ST-segment-elevation myocardial infarction), stent thrombosis/restenosis, or cardiac mortality. Anthropometric, clinical, and pharmacological variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype.

Genealogy of patients with congenital heart disease in isolated populations.

In isolated populations rare genetic diseases are important and relatively frequent. The objective of this study is to determine the geographical aggregates of maternal and paternal ancestors of patients with congenital heart disease (CHD) to determine whether there is an association between the different areas and types of cardiac defects. Descriptive, observational, and cross-sectional study of patients with CHD obtained consecutively in a single adult CHD unit between January 2018 and December 2019 in Gran Canaria (Canary Islands, Spain).

Wilson Disease Prevalence: Discrepancy Between Clinical Records, Registries and Mutation Carrier Frequency.

Objectives: Diagnosis of Wilson disease (WD) is difficult and, as early detection may prevent all symptoms, it is essential to know the exact prevalence to evaluate the cost-efficacy of a screening program. As the number of WD patients was high in our population, we wished to estimate prevalence by determining the carrier frequency for clinically relevant ATP7B mutations.

Methods: To estimate prevalence, screening for the most prevalent mutation was performed in 1661 individuals with ancestry in Gran Canaria, and the frequency of other mutations was estimated from patient records.

COVID-19 quarantine and depression in patients with congenital heart disease.

COVID-19 outbreak has brought tremendous psychological pressure to the general population, especially to those with associated cardiovascular disease. An online Patient Health Questionnaire (PHQ-9) survey on consecutive congenital heart disease (CHD) patients, was carried out to determine depression during the Spanish coronavirus disease (COVID-19) quarantine. Two-hundred forty-two out of 407 (59%) CHD patients answered the survey, 123 (51%) had mild defects, 88 (36%) moderate and 31 (13%) great defects, most of them between 18 and 24 years old and 51% were male.

The effect of physical activity on quality of life and serum glucose and cholesterol levels in patients with congenital heart disease.

As physical activity contributes to quality of life and health, we evaluated its association, as measured by the Global physical activity (GPAQ) questionnaire, on the quality of life (QoL) and serum glucose and cholesterol levels of patients with congenital heart disease (CHD). This cross-sectional study was carried out in 200 adult patients with CHD (17 to 58 years old), of whom 45 had simple defects, 122 moderate defects and 33 great anatomical complexity defects. Physiological complexity was defined as stage A in 74 patients, stage B in 29, stage C in 86 and stage D in 11.

Familial hypercholesterolemia in Gran Canaria: Founder mutation effect and high frequency of diabetes.

Introduction: Gran Canaria is a region of genetic isolation of familial hypercholesterolemia due to a founder mutation, p. [Tyr400_Phe402del], in the LDL receptor (LDLR) gene. Initial data suggest that its carriers could have a high prevalence of diabetes.

Malnutrition is independently associated with an increased risk of major cardiovascular events in adult patients with congenital heart disease.

Background And Aims: Malnutrition is found frequently during chronic diseases, and its prevalence and relation to disease outcome in adult patients with congenital heart disease (CHD) remains unknown.

Methods And Results: A cohort of 393 consecutive stable congenital heart disease (CHD) patients was followed up in a single dedicated clinical unit. Demographic, clinical and laboratory parameters, along with a nutritional risk index (NRI), were studied, as well as major acute cardiovascular events (MACE), defined as arterial thrombotic events, heart failure requiring hospitalization or cardiovascular and non-cardiovascular mortality.

Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity.

Background: Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening.

Red blood cell distribution width in addition to N-terminal prohormone of B-type natriuretic peptide concentration improves assessment of risk of cardiovascular events in adult patients with congenital heart disease.

Background: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in patients with heart disease.

Aim: To establish predictors of high RDW values in patients with congenital heart disease (CHD), and their relationship with cardiovascular events.

Methods: Overall, 561 patients with stable CHD who attended a single outpatient clinic and a matched control population of 2128 patients were studied.

Migrant mobility flows characterized with digital data.

Monitoring migration flows is crucial to respond to humanitarian crisis and to design efficient policies. This information usually comes from surveys and border controls, but timely accessibility and methodological concerns reduce its usefulness. Here, we propose a method to detect migration flows worldwide using geolocated Twitter data.

Prevalence and predictors of psychological distress in congenital heart disease patients.

Objective: To determine psychological distress in congenital heart disease (CHD) patients.

Methods: Cross-sectional study among consecutive CHD patients recruited from a single hospital outpatient clinic to determine anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS) questionnaire.

Results: One hundred and sixty-nine CHD patients [29 (19-39) years old, 100 (59%) males] were studied.

The island of Gran Canaria: A genetic isolate for familial hypercholesterolemia.

Background: Genetic diagnosis of familial hypercholesterolemia (FH) has not been universally performed in the Canary Islands (Spain).

Objectives: This study aimed to genetically characterize a cohort of patients with FH in the island of Gran Canaria.

Methods: Study subjects were 70 unrelated index cases attending a tertiary hospital in Gran Canaria, with a clinical diagnosis of FH, according to the criteria of the Dutch Lipid Clinic Network.

Association between polymorphism rs2032487 in the non-muscle myosin heavy chain IIA gene (MHY9) and chronic kidney disease secondary to type 2 diabetes mellitus in a population of the Canary Islands.

Introduction: Certain polymorphisms in the non-muscle myosin IIA (MYH9) and apolipoprotein L1 (APOL1) genes have been associated to chronic kidney disease (CKD) in different populations. This study examined the association between the MHY9 rs2032487 and APOL1 rs73885319 polymorphisms and advanced CKD related to type 2 diabetes mellitus (T2DM) in a population of Gran Canaria (Canary Islands, Spain).

Patients And Methods: Polymorphisms were genotyped in 152 patients with advanced CKD (estimated glomerular filtration rate [eGFR]<30mL/min/1.

Genetic epidemiology, demographic, and clinical characteristics of Charcot-Marie-tooth disease in the island of Gran Canaria (Spain).

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder. This study involves the entire known CMT patient registry in Gran Canaria, represented by 256 patients belonging to 79 unrelated families, who were clinically and genetically characterized, along with physical and neurophysiological evaluation on 181 and 165 patients, respectively. Complete genotyping showed an estimated prevalence of CMT disease of 30.

CYP2C19 or CYP3A5 Genotyping Does Not Predict Clinical Response to Clopidogrel.

Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events.

Novel Marfan Syndrome-Associated Mutation in the Gene Caused by Parental Mosaicism and Leading to Abnormal Limb Patterning.

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations in the fibrillin-1 () gene. Mutations affecting cysteine residues within the epidermal growith factor-like calcium-binding domains (EGF_CA) of FBN1 are associated with Marfan syndrome features and, especially, with ectopia lentis. We report a novel substitution, affecting the first cysteine of an EGF_CA-binding module encoded by exon 63 of (C2571Y), in a patient presenting with typical Marfan syndrome features but without ectopia lentis.

CYP2C19 activity and cardiovascular risk factors in patients with an acute coronary syndrome.

Introduction: CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of drugs and is involved in the glucocorticoids synthesis. CYP2C19 polymorphisms have been associated with the genetic risk for type 2 diabetes.

Methods: Five hundred and three patients with an acute coronary event were studied to assess the association between the CYP2C19 activity (CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants) and the type of acute coronary syndrome, cardiovascular risk factors (arterial systemic hypertension, diabetes mellitus, dyslipidemia and smoking), analytical parameters and the extent and severity of coronary atherosclerosis.

Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease.

The airway epithelium forms a barrier between the internal and external environments. Epithelial dysfunction is critical in the pathology of many respiratory diseases, including cystic fibrosis. Ets homologous factor (EHF) is a key member of the transcription factor network that regulates gene expression in the airway epithelium in response to endogenous and exogenous stimuli.

Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation.

Background: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability.

Aims: To update disease-causing mutations and current clinical knowledge of the disease.

Materials And Methods: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases.