Irene Plaza Pinto

Screening for Intellectual Disability Using High-Resolution CMA Technology in a Retrospective Cohort from Central Brazil

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.

A non-syndromic intellectual disability associated with a de novo microdeletion at 7q and 18p, microduplication at Xp, and 18q partial trisomy detected using chromosomal microarray analysis approach

BackgroundChromosome 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.ResultsWe 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.ConclusionsOur 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.

The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

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.

Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

BackgroundSupernumerary Marker Chromosomes consist in structurally abnormal chromosomes, considered as an extra chromosome in which around 70% occur as a de novo event and about 30% of the cases are mosaic. Tetrasomy 9p is a rare chromosomal abnormality described as the presence of a supernumerary isochromosome 9p. Clinical features of tetrasomy 9p include a variety of physical and developmental abnormalities.Case presentationHerein, we reported a postnatal case of a newborn who died in early infancy with multiple congenital malformations due to a mosaic de novo tetrasomy 9p detected by Chromosomal Microarray Analysis. Conventional cytogenetics analysis of the proband was 47,XY,+mar[45]/46,XY[5]. The parental karyotypes presented no visible numerical or structural alterations. Microarray Analysis of the proband revealed that the marker chromosome corresponded to a mosaic de novo gain at 9p24.3q21.11.ConclusionsChromosomal Microarray Analysis was helpful to identify the origin of the supernumerary marker chromosome and it was a powerful tool to carry out genetic diagnostic, guiding the medical diagnosis. Furthermore, the CMA allowed observing at the first time in Central Brazil the tetrasomy 9p and partial tetrasomy 9q in mosaic, encompassing a large duplicated region with several morbid genes, in an infant with multiple congenital malformations.

Reward Deficiency Syndrome in Children: Obesity and Metabolic Disorders are Associated with the SNP TaqIA C32806T of the DRD2 Gene

1Núcleo de Pesquisas Replicon, Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil 2Programa de Pós-Graduação Mestrado em Genética, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil 3Programa de Pós-Graduação em Genética e Biologia Molecular, Laboratório de Genética e Biodiversidade, Universidade Federal de Goiás, Goiânia, GO, Brazil 4Laboratório de Citogenética Humana e Genética Molecular, Secretaria do Estado da Saúde de Goiás (LACEN/SESGO), Goiânia, GO, Brazil 5Programa de Pós-Graduação em Biotecnologia e Biodiversidade, Universidade de Brasília, Brasília, DF, Brazil *Corresponding author Renata M. Pinto, MD Núcleo de Pesquisas Replicon Departamento de Biologia Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil E-mail: drarenatamachado@gmail.com