[Genomic newborn screening. Perspective from the Ethics Commission of the Spanish Society for Human Genetics. Part II: Ethical, legal and social issues (ELSIs) of the introduction of next generation sequencing technologies in a public health newborn screening program.].

Genome sequencing is a very attractive technology as it is also the idea of sequencing children at birth, with the aim to establish medical care and preventive actions during their whole life, tailored to the genome of each newborn. Part I of this article analyses limitations and opportunities of next generation sequencing technologies (NGS). Part II relates scientific knowledge with ethical, legal and social issues (ELSIs) concerning its application to a newborn screening program.

[Genomic newborn screening. Perspective from the Ethics commission of the Spanish Society for Human Genetics. Part I. Next generation sequencing technologies applied to newborn screening. Challenges and opportunities.].

In 2003 at the ending of the Human Genome Project, it aroused the idea that all newborns could be sequenced and its genome archived in the clinical record, in order to manage risks of diseases and response to medicaments along his whole life. Eighteen years later, promises of genomic medicine and tremendous decrease of costs of next generation sequencing technologies, continues feeding this dream that shows important practical, ethical and social challenges and genomic sequencing is presented as the next historical change in newborn screening programs. In this paper we analyze challenges and opportunities of next generation sequencing technologies, their real costs, problems associated to management, storage and protection of the enormous amount of genomic data produced and finally, according to conclusions of recent researches, there are considered the conclusions in two contexts, sick newborn with diagnostic purposes and healthy asymptomatic newborns with public health purposes (newborn screening programs).

[Half a century of newborn screening in Spain: Evolution of ethical, legal and social issues (ELSIs). Part III, social issues.].

Decision making for the development of newborn screening programs is based on not only medical but also social concerns and involves different stakeholders. Part III of the article focuses on their role in the governance of the programs. First of all, we consider the proactive role that health authorities has played in the evolution to an evidentiary model of policy development currently based on evidence, just as in the preparation of an expert, impartial and transparent opinion on health policy and its coordination with the national health system.

Recommendations regarding the genetic and immunological study of reproductive dysfunction.

In this article several members of diverse scientific associations and reproduction experts from Spain have updated different genetic and immunological procedure recommendations in couples affected by reproductive dysfunction with the goal of providing a set of useful guidelines for the clinic. The laboratory test has been considered as highly recommendable for making clinical decisions when the result of the diagnostic test is relevant, moderately recommendable when the results are of limited evidence because they are inconsistent, and low when the benefit of the test is uncertain. It is expected that these recommendations will provide some useful guidelines for the diagnosis, prognosis and treatment of couples presenting reproductive dysfunction.

Newborns and low to moderate prenatal environmental lead exposure: might fathers be the key?

This study is part of the BioMadrid Project, a bio-monitoring study designed to assess pollutants in the environment surrounding children born in the Madrid region. Our aim in this report is to evaluate the association between prenatal lead exposure and fetal development using three biological samples (maternal and paternal blood lead at around 34 weeks of gestation as well as cord blood lead levels), three biomarkers of effect in cord blood peripheral lymphocytes (micronucleus in binucleated cells, nucleoplasmic bridges, and nuclear buds), and different anthropometrical characteristics at birth. Maternal and cord blood lead were not associated with newborn measurements or genotoxicity biomarkers.

Development of urologic de novo malignancies after renal transplantation.

Objectives: The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication.

Lead, mercury and cadmium in umbilical cord blood and its association with parental epidemiological variables and birth factors.

Background: In Spain, few studies have evaluated prenatal exposure to heavy metals. The objective of this study was to describe lead, mercury and cadmium concentrations in blood from a sample of newborn-mother-father trios, as well as to investigate the association between metals in cord blood and parental variables. We also explored the relationship between cord blood metal concentrations and child characteristics at birth.

Phenotypic characterization of hereditary epithelial ovarian cancer based on a tissue microarray study.

The pathologic and immunohistochemical features of familial epithelial ovarian cancers are not well understood. We have carried out a comprehensive immunohistochemical study of familial ovarian carcinomas from women with and without BRCA1 or BRCA2 mutations, in order to identify specific and/or common features among these different familial case groups (BRCA1, BRCA2 and non-BRCA1/2) and to identify markers of diagnostic value that might help to select more specific treatments. 73 familial primary ovarian carcinomas were analyzed for the expression of 40 antibodies involved in different genetic pathways using a tissue microarray.

High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease.

[Micronucleus test: cytome assay and health biomarker].

Micronuclei are structures similar to a nucleus but small size and localized in the cytoplasm. A micronucleus contents chromosome fragments or whole chromosomes. The micronucleus test is considered a biomarker for early induced genetic damage.

Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type.

Background: Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.

Mercury, lead and cadmium in human milk in relation to diet, lifestyle habits and sociodemographic variables in Madrid (Spain).

Background: Although breastfeeding is the ideal way of nurturing infants, it can be a source of exposure to toxicants. This study reports the concentration of Hg, Pb and Cd in breast milk from a sample of women drawn from the general population of the Madrid Region, and explores the association between metal levels and socio-demographic factors, lifestyle habits, diet and environmental exposures, including tobacco smoke, exposure at home and occupational exposures.

Methods: Breast milk was obtained from 100 women (20 mL) at around the third week postpartum.

[Cytogenetic biomarkers and health status].

Cytogenetic aberrations are a biomarker for early effect that indicate the cell or the organism has undergone chromosomal damage as a result of his exposure to an external mutagenic/carcinogenic agent. The story begins with the description of the cytogenetic effects of ionizing radiation in 1927, but was not until 1956, with the description of the cytogenetic technique in humans, when genotoxic effects induced by mutagenic or carcinogenic chemical and physical agents are known. Induced chromosomal damage in humans by genotoxic agents is analyzed in human cells in vitro to check the genotoxicity of a suspected agent or in vivo in lymphocytes of individuals exposed to a genotoxic agent.

Cytogenetic status in newborns and their parents in Madrid: the BioMadrid study.

Monitoring cytogenetic damage is frequently used to assess population exposure to environmental mutagens. The cytokinesis-block micronucleus assay is one of the most widely used methods employed in these studies. In the present study we used this assay to assess the baseline frequency of micronuclei in a healthy population of father-pregnant woman-newborn trios drawn from two Madrid areas.

Biomonitoring of exposure to environmental pollutants in newborns and their parents in Madrid, Spain (BioMadrid): study design and field work results.

In Spain environmental surveillance has mainly relied on measures of selected pollutants in air, water, food and soil. A study was conducted in Madrid to assess the feasibility of implementing a surveillance system of exposure among the general population to specific environmental pollutants, using bio-markers. The project was basically focused on the environment surrounding newborns.

Fifty years of cytogenetics: a parallel view of the evolution of cytogenetics and genotoxicology.

A parallelism exists between human cytogenetics and cytogenetic toxicology. The breakthroughs, mostly coming from and used in clinical genetics, are widely used in genetic toxicology. The birth of human cytogenetics occurred in 1956 when it was published that the diploid number of chromosomes in humans is 46.

Loss of the actin regulator HSPC300 results in clear cell renal cell carcinoma protection in Von Hippel-Lindau patients.

Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney. The majority of hereditary and sporadic ccRCC cases are associated with germline and somatic mutations in the Von Hippel-Lindau gene (VHL), respectively. Gross deletions at the VHL locus can result either in ccRCC or in a mild clinical phenotype, with the absence of ccRCC development.

Chromosome 21 tandem repetition and AML1 (RUNX1) gene amplification.

In two patients with hematological neoplasias a tandem repetition of chromosome 21 in the bone marrow was revealed by cytogenetic analysis. The disease was different in the two patients: one was of the lymphoid type, acute lymphoblastic leukemia type L1, and the other was of the myeloid type, acute nonlymphoblastic leukemia type M2. In one case this chromosomal abnormality resulted in amplification of the AML1 gene (HUGO nomenclature: RUNX1), whereas in the other case the AML1 gene was not included in the tandem repetition, showing that apparently similar cytogenetic aberrations may be different at the molecular level.