Potentially toxic element bioaccumulation in consumed indoor shrimp farming associated with diet, water and sediment levels.

Shrimp production is an important industry for many countries and shrimp consumption is increasing worldwide. Shrimps are a highly nutritional food, but can pose a risk for human health if subject to high levels of environmental contaminants. This work studies the presence of As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn in shrimps from Ecuador and compares them to such contents noted in other shrimp-production areas in the world to evaluate the possible risks associated with these elements for consumer health, and to relate them to potentially toxic element (PTE) contents in water, sediments and diets, and also to animal biometric parameters. The PTE levels (mg kg-1 DM) obtained are as follows: in the head-As (3.52-6.11), Cd (0.02-0.10), Co (0.14-0.49) Cr (0.23-4.89), Cu (99.9--233.0), Ni (0.52-1.86), Pb (0.24-1.09), Zn (51.8-100.5) and Hg (µg kg-1 DM) (10.00-66.81); in the tail-(0.91-3.21), Cd (0.01-0.02), Co (0.01-0.43) Cr (0.01-6.52), Cu (20.0-72.44), Ni (0.15-2.03), Pb (0.01-0.69), Zn (31.2-66.1) and Hg (µg kg-1 DM) (10.00-67.18). The concentration of all the PTEs is generally lower than the limits set for seafood by European regulations, except for As in the cephalothorax (4.63 mg kg-1). Different behaviours for PTE accumulation in shrimps were found, which preferentially tend to accumulate in the cephalothorax, except for Hg (40.13 µg kg-1 DM), which accumulates in muscle (body) and is associated with contents of proteins, lipids and total shrimp weight. Nonetheless, the target hazard quotient (THQ) values for PTEs indicate that the consumption of shrimp muscles from Ecuador does not pose a human health risk because the values of these indices are below 1 in all cases.

Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome.

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Partial-UPiD leads to a copy neutral loss of heterozygosity (CN-LOH) of the telomeric region of chromosome 1 (1q41q44), unmasking the potential effect of the mutation detected. The mutation (c.8380dupT) is an insertion located in exon 32 of the LYST gene resulting in a premature stop codon and leading to the loss of all the conserved domains at the C-terminal of the LYST protein. This would account for the severe phenotype observed. We also reviewed the only two previously reported cases of CHS as a result of a uniparental disomy. In this study, we show that the combination of different strategies, including the use of SNP-arrays, is pivotal to fine-tune the diagnosis of rare AR disorders, such as CHS. Moreover, this case highlights the relevance of uniparental disomy as a potential mechanism of CHS expression in non-consanguineous families.

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms.

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, showing sensitivity at least equivalent to that of SNP arrays and higher than that of conventional cytogenetics. In addition, this NGS assay was able to identify both copy-neutral loss of heterozygosity events distributed genome-wide and copy number alterations, as well as somatic mutations within significant driver genes. In summary, we show a novel NGS platform that represents a significant improvement to current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders.

Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.

Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.