THAIS VIRGINIA MOURA MACHADO COSTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Mosaic Trisomy 12 Associated with Overgrowth Detected in Fibroblast Cell Lines(2019) GASPARINI, Yanca; MONTENEGRO, Marilia M.; NOVO-FILHO, Gil M.; CERONI, Jose R. M.; HONJO, Rachel S.; ZANARDO, Evelin A.; DIAS, Alexandre T.; NASCIMENTO, Amom M.; COSTA, Thais V. M. M.; MADIA, Fabricia A.; CHEHIMI, Samar N.; DAMASCENO, Jullian G.; KIM, Chong A.; KULIKOWSKI, Leslie D.Mosaic trisomy 12 is a rare anomaly, and only 9 cases of live births with this condition have been reported in the literature. The clinical phenotype is variable, including neuropsychomotor developmental delay, congenital heart disease, microcephaly, cutaneous spots, facial asymmetry, prominent ears, hypotonia, retinopathy, and sensorineural hearing loss. A 2-year-old female presented with neuropsychomotor developmental delay, prominent forehead, dolichocephaly, patchy skin pigmentation, and unexpected over-growth at birth. Cytogenetic analysis of her peripheral blood showed normal results, suggesting the presence of a chromosomal alteration in other tissues. Further studies using G-banding and FISH performed on fibroblasts from both hyper-and hypopigmented regions identified a 47, XX,+12/46, XX karyo-type. To the best of our knowledge, no patients with mosaic trisomy 12 associated with overgrowth have been reported to date. Congenital overgrowth and neonatal overgrowth have been frequently linked to Pallister-Killian syndrome (PKS; OMIM 601803). This case suggests the possibility of an association of genes present in the 12p region with fetal overgrowth, considering that chromosomal duplications could lead to an increase in the production of aberrant transcripts and disturbing gene dosage effects. This case highlights the importance of cytogenetic analysis in different tissues to provide relevant information to the specific genotype/phenotype correlation. (c) 2019 S. Karger AG, Basel.
- Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases(2020) MONTENEGRO, Marilia M.; QUAIO, Caio R.; PALMEIRA, Patricia; GASPARINI, Yanca; RANGEL-SANTOS, Andreia; DAMASCENO, Julian; NOVAK, Estela M.; GIMENEZ, Thamires M.; YAMAMOTO, Guilherme L.; RONJO, Rachel S.; NOVO-FILHO, Gil M.; CHEHIMI, Samar N.; ZANARDO, Evelin A.; DIAS, Alexandre T.; NASCIMENTO, Amom M.; COSTA, Thais V. M. M.; DUARTE, Alberto J. da S.; COUTINHO, Luiz L.; KIM, Chong A.; KULIKOWSKI, Leslie D.Background Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the & x202f;BLM & x202f;gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is & x202f;still & x202f;not completely understood. Methods We describe two patients confirmed with BS by SCE and molecular analysis. Also, we performed the gene expression profile by the RNA-seq methodology in mRNA transcripts for differential gene expression analysis using as a biological condition for comparison BS versus health controls. Results We detected 216 differentially expressed genes related to immunological pathways such as positive regulation and activation of B cells, immune effector process and absence of difference of DNA repair genes expression. In addition; we also observed differentially expressed genes associated with apoptosis control, such as BCL2L1, CASP7, CDKN1A, E2F2, ITPR, CD274, TNFAIP6, TNFRSF25, TNFRSF13C, and TNFRSF17. Conclusion Our results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA-seq.
- Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability(2016) NOVO-FILHO, Gil M.; MONTENEGRO, Marilia M.; ZANARDO, Evelin A.; DUTRA, Roberta L.; DIAS, Alexandre T.; PIAZZON, Flavia B.; COSTA, Tais V. M. M.; NASCIMENTO, Amom M.; HONJO, Rachel S.; KIM, Chong A.; KULIKOWSKI, Leslie D.The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases. (C) 2016 S. Karger AG, Basel
- Rare Genomic Rearrangement in a Boy with Williams-Beuren Syndrome Associated to XYY Syndrome and Intriguing Behavior(2015) DUTRA, Roberta L.; PIAZZON, Flavia B.; ZANARDO, Evelin A.; COSTA, Thais Virginia Moura Machado; MONTENEGRO, Marilia M.; NOVO-FILHO, Gil M.; DIAS, Alexandre T.; NASCIMENTO, Amom M.; KIM, Chong Ae; KULIKOWSKI, Leslie D.Williams-Beuren syndrome (WBS) is caused by a hemizygous contiguous gene microdeletion of 1.55-1.84 Mb at 7q11.23 region. Approximately, 28 genes have been shown to contribute to classical phenotype of SWB with presence of dysmorphic facial features, supravalvular aortic stenosis (SVAS), intellectual disability, and overfriendliness. With the use of Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques, is possible define with more accuracy partial or atypical deletion and refine the genotype-phenotype correlation. Here, we report on a rare genomic structural rearrangement in a boy with atypical deletion in 7q11.23 and XYY syndrome with characteristic clinical signs, but not sufficient for the diagnosis of WBS. Cytogenetic analysis of G-banding showed a karyotype 47, XYY. Analysis of DNA with the technique of MLPA (Multiplex Ligation-dependent Probe Amplification) using kits a combination of kits (P064, P036, P070, and P029) identified an atypical deletion on 7q11.23. In addition, high resolution SNP Oligonucleotide Microarray Analysis (SNP-array) confirmed the alterations found by MLPA and revealed others pathogenic CNVs, in the chromosomes 7 and X. The present report demonstrates an association not yet described in literature, between Williams-Beuren syndrome and 47, XYY. The identification of atypical deletion in 7q11.23 concomitant to additional pathogenic CNVs in others genomic regions allows a better comprehension of clinical consequences of atypical genomic rearrangements. (C) 2015 Wiley Periodicals, Inc.
- Breakpoint delineation in 5p- patients leads to new insights about microcephaly and the typical high-pitched cry(2020) CHEHIMI, Samar N.; ZANARDO, Evelin A.; CERONI, Jose R. M.; NASCIMENTO, Amom M.; MADIA, Fabricia A. R.; DIAS, Alexandre T.; FILHO, Gil M. N.; MONTENEGRO, Marlia M.; DAMASCENO, Jullian; COSTA, Thas V. M. M.; GASPARINI, Yanca; KIM, Chong A.; KULIKOWSKI, Leslie D.Background Cri du chat syndrome (CdCS) is a rare syndrome caused by a partial or complete deletion of the short arm of chromosome 5 (5p-). The main clinical features include a high-pitched cry, facial asymmetry, microcephaly, round face at birth, epicanthal folds, hypotonia, delayed growth and development. Methods We studied 14 Brazilian patients with CdCS using genomic array in order to better define the 5p breakpoints and recognize copy number variations (CNVs) that contribute to clinical manifestations associated with the syndrome. Results Array confirmed terminal deletions in 13 patients and an interstitial deletion in one patient. It was also possible to map the breakpoints and associate a genomic region of 4.7 Mb to the development of head circumference and cat-like cry. We also found other CNVs concomitant to the 5p deletion including a 9p duplication, a 17q deletion, and a 22q deletion in three different patients. Conclusion With advancements of molecular cytogenomic methods in the last two decades, it was possible to evidence cryptic alterations and improve the genotype-phenotype correlation. In this work, we describe a new genomic region associated with microcephaly and cat-like cry and highlight the importance of precise delineation of 5p deletion breakpoints and detection of other CNVs in CdCS patients to improve genotype-phenotype correlation to perform a complete clinical and molecular diagnosis.