Unique Genetic Profiles in Hypertrophic Cardiomyopathy Patients From São Miguel Island (Azores, Portugal).

To investigate the clinical features and mutational spectrum underlying hypertrophic cardiomyopathy (HCM) in São Miguel Island (Azores, Portugal), we analyzed 37 adult patients (12 sporadic, 25 familial) with positive genetic tests. Seven disease-causing variants were identified, being two novels, in three sarcomeric genes (MYH7, TNNT2, and MYBPC3) and one non-sarcomeric gene (ALPK3). The novel variants, classified as likely pathogenic (LP), involved large multi-exon deletions in MYBPC3 (exons 26-32 and 28-33).

Seroprevalence of Protective Antibodies Against Influenza and the Reduction of the Influenza Incidence Rate: An Annual Repeated Cross-Sectional Study From 2014 to 2019.

Background: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate.

Methods: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal.

Enzyme immunoassays (EIA) for serodiagnosis of human leptospirosis: specific IgG3/IgG1 isotyping may further inform diagnosis of acute disease.

The laborious microscopic agglutination test (MAT) is the gold standard serologic test for laboratory diagnosis of leptospirosis. We developed EIA based serologic assays using recombinant proteins (rLigA, rLigB, rLipL32) and whole-cell extracts from eight Leptospira serovars as antigen and assessed the diagnostic performance of the new assay within each class, against MAT positive (MAT+) human sera panels from Portugal/PT (n = 143) and Angola/AO (n = 100). We found that a combination of recombinant proteins rLigA, rLigB and rLipL32 correctly identified antigen-specific IgG from patients with clinical and laboratory confirmed leptospirosis (MAT+) with 92% sensitivity and ~ 97% specificity (AUC 0.

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed.

A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal).

Background: Early diagnosis and treatment are improving significantly the quality of life of patients with cystic fibrosis (CF). This recessive disease is caused by a great variability of mutations in the CF transmembrane conductance (CFTR) gene, whose spectrum and frequency can be different across populations.

Methods: We performed a retrospective cross-sectional study of CF patients from the island of São Miguel (Azores, Portugal) through a clinical, genealogical, genetic and epidemiological investigation.

A rare case of a primary retroperitoneal mucinous cystic tumour with borderline malignancy and literature review.

Primary retroperitoneal mucinous cystic neoplasms (PRMCN) with borderline malignancy are exceptionally rare tumours with lack of pathognomonic clinical and imaging-specific features. Here, we report a case of PRMCN with borderline malignancy in a 62-year-old woman who presented with abdominal pain. Imaging studies revealed a well-defined cystic mass on the right flank in close relation with the cecum and caecal appendix, without other findings suggestive of malignancy.

Yoga in primary health care: A quasi-experimental study to access the effects on quality of life and psychological distress.

Background: and purpose: Yoga is growing in popularity, but its benefits and integration into primary care remain uncertain. Here, we determine yoga effects on quality of life and psychological distress, and evaluate the feasibility of introducing yoga at primary care level.

Materials And Methods: This is a prospective, longitudinal, quasi-experimental study, with an intervention (n = 49) and a control group (n = 37).

Prenatal sonographic diagnosis of isolated fetal ascites in cri-du-chat (5p-) syndrome: A case report.

Isolated fetal ascites and cri-du-chat syndrome (CdCS; OMIM #123450) are two very rare conditions that, to our best knowledge, have never been reported together. Here, we describe a case of isolated fetal ascites detected in the first trimester ultrasound, with no other remarkable signs. After an extensive work-up (fetal ultrasound, serologies, Coombs test, and NIPT), an amniocentesis was performed and revealed an abnormal karyotype of 46,XX,del(5)(p15.

Diagnosis of Human Leptospirosis in a Clinical Setting: Real-Time PCR High Resolution Melting Analysis for Detection of Leptospira at the Onset of Disease.

Currently, direct detection of Leptospira can be done in clinical laboratories by conventional and by real-time PCR (qRT-PCR). We tested a biobank of paired samples of serum and urine from the same patient (202 patients) presenting at the hospital in an area endemic for leptospirosis using qRT-PCR followed by high resolution melting (HRM) analysis. The results were compared with those obtained by conventional nested PCR and with the serologic gold standard microscopic agglutination test (MAT).

A Clinical Roadmap to Investigate the Genetic Basis of Pediatric Pheochromocytoma: Which Genes Should Physicians Think About?

Pheochromocytoma is very rare at a pediatric age, and when it is present, the probability of a causative genetic mutation is high. Due to high costs of genetic surveys and an increasing number of genes associated with pheochromocytoma, a sequential genetic analysis driven by clinical and biochemical phenotypes is advised. The published literature regarding the genetic landscape of pediatric pheochromocytoma is scarce, which may hinder the establishment of genotype-phenotype correlations and the selection of appropriate genetic testing at this population.

A novel PLEC nonsense homozygous mutation (c.7159G > T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

Background: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disease, characterized mainly by skin blistering at birth or shortly thereafter, progressive muscle weakness, and rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM *601282), which encodes plectin, a structural protein expressed in several tissues, including epithelia and muscle. We describe a patient affected with EBS-MD and diffuse alopecia in which we identified a novel pathogenic mutation by PCR amplification of all coding exons and exon-intron boundaries of PLEC gene, followed by bidirectional Sanger sequencing.

Mitochondrial DNA analysis of Tunisians reveals a mosaic genetic structure with recent population expansion.

Tunisia is a country of great interest for human population genetics due to its strategic geographic position and rich human settlement history. These factors significantly contributed to the genetic makeup of present-day Tunisians harbouring components of diverse geographic origins. Here, we investigated the genetic structure of Tunisians by performing a mitochondrial DNA (mtDNA) comparison of 15 Tunisian population groups, in order to explore their complex genetic landscape.

Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with mutations. Functional analyses were performed in oocytes for eight missense and two nonsense mutations.

Cross-protection to new drifted influenza A(H3) viruses and prevalence of protective antibodies to seasonal influenza, during 2014 in Portugal.

Introduction: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population.

Genealogical and molecular analysis of a family-based cohort of congenital heart disease patients from the São Miguel Island (Azores, Portugal).

Background: Congenital heart disease (CHD) is one common birth malformation, accounting for ∼30% of total congenital abnormalities.

Aim: Considering the unknown role of consanguinity in causing CHD, this study hypothesised that consanguineous unions and/or familial aggregation may be frequent in the Azorean Island of São Miguel (Portugal). To that end, a retrospective observational study was performed based on genealogical and molecular analyses.

Molecular diagnosis of infectious diseases in São Miguel Island (Azores, Portugal): A hospital-based descriptive study.

Introduction: We performed a descriptive analysis of molecular diagnosis of infectious agents in the São Miguel Island population, in order to address questions like what is the frequency of clinical requests, is it observable seasonality of pathogens, and what is the positive rate for the clinical diagnosis.

Methodology: This was a retrospective and descriptive study based on 878 individuals suspected of harboring infectious diseases during two consecutive years, 2012-2013. More than 25 different pathogens were investigated by polymerase chain reaction (PCR)-based methods.

Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls.

Paternal Transmission of Small Supernumerary Marker Chromosome 15 Identified in Prenatal Diagnosis Due to Advanced Maternal Age.

The detection of supernumerary marker chromosomes (SMCs) in prenatal diagnosis is always a challenge. In this study, we report a paternally inherited case of a small SMC(15) that was identified in prenatal diagnosis due to advanced maternal age. A 39-year-old woman underwent amniocentesis at 16 weeks of gestation.

Carriers of the Complex Allele HFE c.[187C>G;340+4T>C] Have Increased Risk of Iron Overload in São Miguel Island Population (Azores, Portugal).

Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.

A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.

Background: The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances.

Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters.

Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: A pilot study.

The imbalance between reactive oxygen species (ROS) production and their elimination by antioxidants leads to oxidative stress. Depending on their concentration, ROS can trigger apoptosis or stimulate cell proliferation. We hypothesized that oxidative stress and mitochondrial dysfunction may participate not only in apoptosis detected in some myelodysplastic syndrome (MDS) patients, but also in increasing proliferation in other patients.

Screening of copy number variants in the 22q11.2 region of congenital heart disease patients from the São Miguel Island, Azores, revealed the second patient with a triplication.

Background: The rearrangements in the 22q11.2 chromosomal region, responsible for the 22q11.2 deletion and microduplication syndromes, are frequently associated with congenital heart disease (CHD).