Mercury Contamination: A Growing Threat to Riverine and Urban Communities in the Brazilian Amazon.

In recent decades, widespread and uncontrolled use of mercury (Hg) in artisanal small-scale gold mining has released thousands of tons of mercury-contaminated waste in the Amazon biome, endangering the largest tropical rainforest worldwide. In this study, we assessed and compared blood Hg levels in individuals living in urban and riverine areas in the lower Tapajós basin and examined the association between Hg exposure and specific biochemical parameters. In total, 462 adults from eight riverine communities and one urban area were assessed. Overall, 75.6% of the participants exhibited Hg concentrations exceeding the safe limit (10 µg/L). Hg exposure was higher in the riverine population (90%) than in urban areas (57.1%). Mean Hg levels were 21.8 ± 30.9 µg/L and 50.6 µg/L in urban and riverine residents, respectively. The mean Hg level was higher in those aged 41-60 years in both urban and riparian areas, with riparian residents exhibiting a mean double that of urban residents. The highest glucose and hepatic biomarker levels were detected in the urban area, whereas the highest levels of renal biomarker occurred in the riverine population. Our results indicate that Hg contamination remains a persistent challenge for the urban population of Santarém, a major city in the Brazilian Amazon.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 µg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Health Risk Assessment of Mercury Exposure from Fish Consumption in Munduruku Indigenous Communities in the Brazilian Amazon.

Fish serves as the principal source of animal protein for the indigenous people of the Amazon, ensuring their food and nutritional security. However, gold mining causes mercury (Hg) contamination in fish, and consequently increases health risks associated with fish consumption. The aim of this study was to assess the health risk attributed to the consumption of mercury-contaminated fish by Munduruku indigenous communities in the Middle-Tapajós Region. Different fish species were collected in the Sawré Muybu Indigenous Land to determine mercury levels. The health risk assessment was carried out according to the World Health Organization (WHO 2008) methodology and different scenarios were built for counterfactual analysis. Eighty-eight fish specimens from 17 species and four trophic levels were analyzed. Estimates of Hg ingestion indicated that the methylmercury daily intake exceeds the U.S. EPA (United States Environmental Protection Agency) (2000) reference dose from 3 to 25-fold, and up to 11 times the FAO (Food and Agriculture Organization)/WHO (2003) dose recommendation. In all situations analyzed, the risk ratio estimates were above 1.0, meaning that the investigated Munduruku communities are at serious risk of harm as a result of ingestion of mercury-contaminated fish. These results indicate that, at present, fish consumption is not safe for this Munduruku population. This hazardous situation threatens the survival of this indigenous population, their food security, and their culture.

Beckwith-Wiedemann syndrome and uniparental disomy 11p: fine mapping of the recombination breakpoints and evaluation of several techniques.

Beckwith-Wiedemann syndrome (BWS) is a phenotypically and genotypically heterogeneous overgrowth syndrome characterized by somatic overgrowth, macroglossia and abdominal wall defects. Other usual findings are hemihyperplasia, embryonal tumours, adrenocortical cytomegaly, ear anomalies, visceromegaly, renal abnormalities, neonatal hypoglycaemia, cleft palate, polydactyly and a positive family history. BWS is a complex, multigenic disorder associated, in up to 90% of patients, with alteration in the expression or function of one or more genes in the 11p15.5 imprinted gene cluster. There are several molecular anomalies associated with BWS and the large proportion of cases, about 85%, is sporadic and karyotypically normal. One of the major categories of BWS molecular alteration (10-20% of cases) is represented by mosaic paternal uniparental disomy (pUPD), namely patients with two paternally derived copies of chromosome 11p15 and no maternal contribution for that. In these patients, in addition to the effects of IGF2 overexpression, a decreased level of the maternally expressed gene CDKN1C may contribute to the BWS phenotype. In this paper, we reviewed a series of nine patients with BWS because of pUPD using several methods with the aim to evaluate the percentage of mosaicism, the methylation status at both loci, the extension of the pUPD at the short arm and the breakpoints of recombination. Fine mapping of mitotic recombination breakpoints by single-nucleotide polymorphism-array in individuals with UPD and fine estimation of epigenetic defects will provide a basis for understanding the aetiology of BWS, allowing more accurate prognostic predictions and facilitating management and surveillance of individuals with this disorder.

Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism.

Molecular studies in a patient with Beckwith-Wiedemann syndrome phenotype who developed two different tumours revealed an unexpected observation of almost complete loss of heterozygosity of all chromosomes. It is shown, by means of numerous molecular methods, that the absence of maternal contribution in somatic cells is due to high-degree (∼ 85%) genome-wide paternal uniparental disomy (UPD). The observations indicate that the genome-wide UPD results from diploidisation, and have important implications for genetic counselling and tumour surveillance for the growing number of UPD associated imprinting disorders.

CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by macroglossia, macrosomia, and abdominal wall defects. It is a multigenic disorder caused in most patients by alterations in growth regulatory genes. A small number of individuals with BWS (5-10%) have mutations in CDKN1C, a cyclin-dependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation. Here, we report on eight patients with BWS and CDKN1C mutations and review previous reported cases. We analyzed 72 patients (50 BWS, 17 with isolated hemihyperplasia (IH), three with omphalocele, and two with macroglossia) for CDKN1C defects with the aim to search for new mutations and to define genotype-phenotype correlations. Our findings suggest that BWS patients with CDKN1C mutations have a different pattern of clinical malformations than those with other molecular defects. Polydactyly, genital abnormalities, extra nipple, and cleft palate are more frequently observed in BWS with mutations in CDKN1C. The clinical observation of these malformations may help to decide which genetic characterization should be undertaken (i.e., CDKN1C screening), thus optimizing the laboratory evaluation for BWS.

No association of the polyhistidine tract polymorphism of the ZIC2 gene with neural tube defects in a South American (ECLAMC) population.

The ZIC genes comprise a family of transcriptional factors associated with neural tube defects (NTDs) in mice and with holoprosencephaly in humans. An allelic variant of ZIC2, a CAC repeat within the first exon, was reported in association with an increased risk of non-syndromic NTDs in patients with a Hispanic ethnic background. We investigated whether this 10-residue histidine tract polymorphism of the ZIC2 gene (c.718_720dupCAC) was associated with the risk of NTDs in a sample of 138 patients and their parents from the Latin American Collaborative Study of Congenital Malformations (ECLAMC) hospital network. Analysis with log-linear models of 138 family triads of mother, father and affected child did not provide evidence to support the notion that case (or maternal) 10H/10H or -/10H genotypes were associated with NTDs in this South American population sample, where the 10H variant occurred in 5% of newborns affected with NTDs. We also described the first example of the homozygous state of the 10H allele in a patient with cephalocele, holoprosencephaly and microphthalmia, but did not ascertain whether this polymorphism is associated with the increased risk of a specific subgroup of NTDs, as a normal father of a patient with anencephaly presented the same genotype.