PIGN c.776T>C (p.Phe259Ser) variant present in trans with a pathogenic variant for PIGN-congenital disorder of glycosylation: Bella-Noah syndrome.

Glycosylation is the most common protein and lipid post-translational modification in humans. Congenital disorders of glycosylation (CDG) are characterized by both genetic and clinical heterogeneity, presenting multisystemic manifestations, and in most cases are autosomal recessive in inheritance. The PIGN gene is responsible for the addition of phosphoethanolamine to the first mannose in the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, a highly conserved process that enables proteins to bind to the cell surface membrane. Here, we report a family with two siblings pediatric cases with the exact same compound heterozygous variants in PIGN. The (c.776T > C) variant of uncertain significance (VUS) together with a known pathogenic variant (c.932T > G), resulting in clinical features compatible with PIGN-related conditions, more specific the CDG. This is the first time that PIGN variant c.776T > C is reported in literature in individuals with PIGN-congenital disorder of glycosylation (PIGN-CDG), and the current submission in ClinVar by Invitae® is specifically of our case. Detailed clinical information and molecular analyses are presented. Here, we show for the first time two affected siblings with one pathogenic variant (c.932T > G) and the c.776T > C VUS in trans. In honor of the family, we propose the name Bella-Noah Syndrome for disorder.

Factors associated with hospitalization in the acute phase of Chikungunya.

OBJECTIVE: Determine characteristics associated with hospitalization in the acute phase of Chikungunya. METHODS: Cross-sectional study including data on Chikungunya cases reported in Vitória, Espírito Santo state, Brazil, between March 2016 and December 2021. RESULTS: Hospitalizations accounted for 1.42% (n = 41) of the 2,868 cases included. There were statistically significant differences between hospitalized and non-hospitalized regarding age (P 0.001), which was lower among hospitalized patients, and pregnancy, which was more frequent in the hospitalized group (P 0.010). Patients younger than two years old and older than 65 years corresponded to 31.7% of hospitalizations. Back pain (OR = 0.134; 95% CI = 0.044-0.409) and arthralgia (OR = 0.226; 95% CI = 0.083-0.613) were protective factors for hospitalization. CONCLUSION: Groups at risk of severe Chikungunya, including those under two and over 65 years of age, may require more hospitalization, even with milder manifestations.

Biomarkers in Breast Cancer: An Old Story with a New End.

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.

FADS1 and FADS2 Gene Polymorphisms Modulate the Relationship of Omega-3 and Omega-6 Fatty Acid Plasma Concentrations in Gestational Weight Gain: A NISAMI Cohort Study.

The polymorphisms of fatty acid desaturase genes FADS1 and FADS2 have been associated with an increase in weight gain. We investigated FADS1 and FADS2 gene polymorphisms and the relation between ω-3 and ω-6 fatty acid plasma concentrations and gestational weight gain. A prospective cohort study of 199 pregnant women was followed in Santo Antônio de Jesus, Brazil. Plasma levels of polyunsaturated fatty acids (PUFAs) were measured at baseline and gestational weight gain during the first, second, and third trimesters. Fatty acid recognition was carried out with the aid of gas chromatography. Single nucleotide polymorphisms (SNPs) were genotyped using real-time PCR. Statistical analyses included Structural Equation Modelling. A direct effect of FADS1 and FADS2 gene polymorphisms on gestational weight was observed; however, only the SNP rs174575 (FADS2) showed a significant positive direct effect on weight over the course of the pregnancy (0.106; p = 0.016). In terms of the influence of SNPs on plasma levels of PUFAs, it was found that SNP rs174561 (FADS1) and SNP rs174575 (FADS2) showed direct adverse effects on plasma concentrations of ω-3 (eicosapentaenoic acid and alpha-linoleic acid), and only SNP rs174575 had positive direct effects on plasma levels of ARA and the ARA/LA (arachidonic acid/linoleic acid) ratio, ω-6 products, while the SNP rs3834458 (FADS2) had an adverse effect on plasma concentrations of EPA, leading to its increase. Pregnant women who were heterozygous and homozygous for the minor allele of the SNP rs3834458 (FADS2), on the other hand, showed larger concentrations of series ω-3 substrates, which indicates a protective factor for women's health.

A view of the maternal inheritance of Espírito Santo populations: The contrast between the admixed and Pomeranian descent groups.

In addition to its valuable utility in forensic investigations, mitochondrial DNA (mtDNA) analysis is a reliable tool to uncover the origins of admixed populations, such as Brazilians. The state of Espírito Santo (ES), similar to other coastal Brazilian states, has a population shaped by 3 main ancestral roots: Amerindian, African and European. Among the latter, the Pomeranian descendants stand out due to the preservation of the traditional aspects of their culture, especially the Pomeranian language. Despite the genetic data already available, there is no mtDNA database that adequately reflects the diversity, the geographic distribution, and the origins of the maternal lineages from ES. To increase the knowledge of maternal ancestry and to investigate the population's genetic stratification, a total of 291 samples were collected in the 4 macroregions (Metropolitan, South, Central and North) of ES and in the Pomeranian communities. Complete control region data were produced for the general (N=214) and Pomeranian (N=77) groups. Regarding the general population, the high values of haplotype diversity (H=99.9%) and pairwise differences (MNPD=16.9) found are in agreement with those reported for other populations in the southeast region of the country. Regarding maternal inheritance, the ES populations stood out due to the predominance of European haplogroups (49.5%), although the North macroregion had a higher African ancestry (47.1%). Among the Pomeranians, the lowest MNPD value (11.2) and the high percentage of shared haplotypes (15%) were indicative of founder events. The FST analysis showed that the Pomeranians (98.7% of European lineages) are genetically isolated from the other admixed populations in Brazil. This study demonstrated that the ES state contains singularities regarding the intrapopulational and interpopulational diversity of mtDNA. Even after 5 centuries of interethnic admixture, the present-day population of Espírito Santo harbors genetic marks that trace back to the historical aspects of its formation.

Association study of the BIN1 and IL-6 genes on Alzheimer's disease.

Genome-wide association study (GWAS) has identified several novel genes associated with the risk of Alzheimer's disease (AD), which is a progressive neurodegenerative disease in elders. However, most of the novel genes have not been validated through replication in separated populations. Among them, the BIN1 gene is involved in endocytosis and intracellular trafficking as well as in the formation of ß amyloid plaques and neurofibrillary tangles, which are the main pathological hallmarks of AD. The IL-6 gene has also been frequently associated with AD; however, consistent results have not been found. IL-6, a cytokine from the immune system, is implicated in the pathogenesis of several degenerative diseases. Similar to BIN1, it is suggested that IL-6 is also involved in the formation of ß amyloid plaques. In this case-control study, we aimed to investigate whether single nucleotide polymorphisms in the BIN1 (rs744373) and IL-6 (rs1800795) genes are associated with AD. Genotype frequencies were evaluated via PCR-RFLP in 82 late-onset AD patients and 159 elderly healthy controls, who were matched by age and gender. In this study, no association was found for either polymorphism, suggesting that these genes are not implicated in the aetiology of AD in all populations.