Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome.

OBJECTIVES: Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. METHODS: The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. RESULTS: The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. CONCLUSIONS: The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases.

Metabolomics as a potential tool for the diagnosis of growth hormone deficiency (GHD): a review.

Metabolomics uses several analytical tools to identify the chemical diversity of metabolites present in organisms. These metabolites are low molecular weight molecules (<1500 Da) classified as a final or intermediary product of metabolic processes. The application of this omics technology has become prominent in inferring physiological conditions through reporting on the phenotypic state; therefore, the introduction of metabolomics into clinical studies has been growing in recent years due to its efficiency in discriminating pathophysiological states. Regarding endocrine diseases, there is a great interest in verifying comprehensive and individualized physiological scenarios, in particular for growth hormone deficiency (GHD). The current GHD diagnostic tests are laborious and invasive and there is no exam with ideal reproducibility and sensitivity for diagnosis neither standard GH cut-off point. Therefore, this review was focussed on articles that applied metabolomics in the search for new biomarkers for GHD. The present work shows that the applications of metabolomics in GHD are still limited, since the little complementarily of analytical techniques, a low number of samples, GHD combined to other deficiencies, and idiopathic diagnosis shows a lack of progress. The results of the research are relevant and similar; however, their results do not provide an application for clinical practice due to the lack of multidisciplinary actions that would be needed to mediate the translation of the knowledge produced in the laboratory, if transferred to the medical setting.

Metabolic profiling of organic acids in urine samples of Cri Du Chat syndrome individuals by gas chromatography-mass spectrometry.

Cri Du Chat (CDC) syndrome is a rare genetic condition caused by the deletion of genetic material on the small arm (the p arm) of chromosome 5. A high-pitched cry that sounds like that of a cat, dysmorphic characteristics, and cytogenetic methods are often used for diagnosing the syndrome. In this study, we applied GC-MS analysis for determining organic acids in urine from 17 control volunteers without CDC syndrome, and from 16 individuals with the CDC syndrome in order to determine the profile of organic acids and biochemical pathways alterations resulting from this genetic condition. First, performing multivariate data analysis selected the best method for extracting organic acids with greater signal intensities and good reproducibility. After selection, multivariate (PLS-DA) and univariate (Mann-Whitney test) data analysis discriminated the metabolites responsible for separation between groups. Nine organic acid metabolites had values of VIP ≥ 1.0 and p-values ≤ 0.05, with highest intensities in the samples from CDC individuals, indicating the strongest discriminative power (tricarballylic acid, indoleacetic acid, anthranilic acid, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 4-hydroxyhippuric acid, pantothenic acid, homovanillic acid, and vanillylmandelic acid). These metabolites are involved in several biochemical pathways like in the tyrosine and phenylalanine metabolism, as well as the tryptophan metabolism, which could be associated (i) to some neuropsychiatric alterations commonly observed in CDC individuals, (ii) to exogenous compounds related to transformation products by intestinal microbial, and (iii) to a possible deficiency in enzyme activity due to the syndrome.

Lead exposure from households and school settings: influence of diet on blood lead levels.

Lead is known as a potent toxicant to human health, particularly for children while their central nervous system is developing. The aim of this study was to investigate the associations between blood lead levels (BLLs) and lead exposure in the children's diet, home, and school environments. A cross-sectional study was conducted with 153 children aged 1-4 years, in four day care centers (DCCs), where a high prevalence of lead exposure was previously found. Lead determination by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64). Environmental screenings were conducted to evaluate lead concentrations in the tableware, buildings, and playground items in all DCCs and children's homes (n = 18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean was 2.71 µg dL-1. Means for 24-h lead concentrations in the diet were 1.61 and 2.24 µg kg-1 of body weight (BW) in two DCCs. Lead concentrations in the water supply were lower than 2 µg L-1. More than 11% of the DCCs' environmental analyses presented lead concentrations higher than or equal to 1 mg cm-2, as defined by the USEPA. The diet was not found to be a risk factor for lead exposure, but households and DCC settings raised concern. Children's exposure to lead in DCC environments, where they spend the most part of their weekdays, appeared to be relevant. Graphical abstract ᅟ.