RESUMEN
Myelodysplastic syndrome (MDS) is an onco-hematologic disease with distinct levels of peripheral blood cytopenias, dysplasias in cell differentiation and various forms of chromosomal and cytogenomic alterations. In this study, the Chromosomal Microarray Analysis (CMA) was performed in patients with primary MDS without numerical and/or structural chromosomal alterations in karyotypes. A total of 17 patients was evaluated by GTG banding and eight patients showed no numerical and/or structural alterations. Then, the CMA was carried out and identified gains and losses CNVs and long continuous stretches of homozygosity (LCSHs). They were mapped on chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 14, 16, 17, 18, 19, 20, 21, X, and Y. Ninety-one genes that have already been implicated in molecular pathways important for cell viability were selected and in-silico expression analyses demonstrated 28 genes differentially expressed in mesenchymal stromal cells of patients. Alterations in these genes may be related to the inactivation of suppressor genes or the activation of oncogenes contributing to the evolution and malignization of MDS. CMA provided additional information in patients without visible changes in the karyotype and our findings could contribute with additional information to improve the prognostic and personalized stratification for patients.
Asunto(s)
Síndromes Mielodisplásicos/genética , Adulto , Anciano , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Cariotipo , Masculino , Persona de Mediana EdadRESUMEN
The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.
Asunto(s)
Mapeo Cromosómico/métodos , Variaciones en el Número de Copia de ADN/genética , Síndrome de DiGeorge/genética , Duplicación de Gen/genética , Pruebas Genéticas/métodos , Adolescente , Niño , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 22/genética , Femenino , Marcadores Genéticos/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodosRESUMEN
Intellectual disability is a complex, variable, and heterogeneous disorder, representing a disabling condition diagnosed worldwide, and the etiologies are multiple and highly heterogeneous. Microscopic chromosomal abnormalities and well-characterized genetic conditions are the most common causes of intellectual disability. Chromosomal Microarray Analysis analyses have made it possible to identify putatively pathogenic copy number variation that could explain the molecular etiology of intellectual disability. The aim of the current study was to identify possible submicroscopic genomic alterations using a high-density chromosomal microarray in a retrospective cohort of patients with otherwise undiagnosable intellectual disabilities referred by doctors from the public health system in Central Brazil. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had intellectual disability and a normal karyotype. The analysis detected 18 CNVs in 60% of patients. Pathogenic CNVs represented about 22%, so it was possible to propose the etiology of intellectual disability for these patients. Likely pathogenic and unknown clinical significance CNVs represented 28% and 50%, respectively. Inherited and de novo CNVs were equally distributed. We report the nature of CNVs in patients from Central Brazil, representing a population not yet screened by microarray technologies.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos/genética , Variaciones en el Número de Copia de ADN/genética , Discapacidad Intelectual/genética , Adulto , Brasil , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Cariotipificación , Análisis por Micromatrices/métodos , Persona de Mediana EdadRESUMEN
BACKGROUND: Chromosome abnormalities that segregate with a disease phenotype can facilitate the identification of disease loci and genes. The relationship between chromosome 18 anomalies with severe intellectual disability has attracted the attention of cytogeneticists worldwide. Duplications of the X chromosome can cause intellectual disability in females with variable phenotypic effects, due in part to variations in X-inactivation patterns. Additionally, deletions of the 7qter region are associated with a range of phenotypes. RESULTS: We report the first case of de novo microdeletion at 7q and 18p, 18q partial trisomy, microduplication at Xp associated to intellectual disability in a Brazilian child, presenting a normal karyotype. Karyotyping showed any chromosome alteration. Chromosomal microarray analysis detected a de novo microdeletion at 18p11.32 and 18q partial trisomy, an inherited microdeletion at 7q31.1 and a de novo microduplication at Xp22.33p21.3. CONCLUSIONS: Our report illustrates a case that presents complex genomic imbalances which may contribute to a severe clinical phenotypes. The rare and complex phenotypes have to be investigated to define the subsets and allow the phenotypes classification.
RESUMEN
This study evaluated the variability of GSTM1 and GSTT1 polymorphisms in individuals occupationally exposed to pesticides in ten Goias municipalities that present intense agricultural activity. We evaluated blood samples of 235 individuals, which 120 were rural workers occupationally exposed to pesticides and 115 formed the control group, analyzing GST polymorphisms by quantitative polymerase chain reaction (qPCR).The exposed group consisted of 111 men and nine women only getting an average of 39 ± 9 years. These workers were from ten rural municipalities situated at Goias state. It was found that 18 % of the exposed individuals had the GSTT1 null genotype and 49 % had the GSTM1 null genotype, and 10 % had both null genotypes. Data as intoxication (42 %), use of Personal Protection Equipment (PPE; 52 %) and if the worker prepared the pesticide (7 %), or if just applied the pesticide (22 %) or if the worker prepared and applied (71 %) have all been correlated with genetic polymorphisms. There were no statistically significant differences between the GSTM1 and GSTT1 polymorphisms between control and exposed groups. Finally, we could not associate a null GSTT1 or null GSTM1 polymorphisms or both to intoxication events caused by pesticides, but instead we presented the importance to use PPE to prevent such harm, once we found a statistically significant association between the use of PPE and events of intoxication (p ≤ 0.001).