AMOM MENDES NASCIMENTO
Projetos de Pesquisa
Unidades Organizacionais
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
22 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 22
- Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p(2023) ALMEIDA, Vanessa T.; CHEHIMI, Samar N.; GASPARINI, Yanca; NASCIMENTO, Amom M.; CARVALHO, Gleyson F. S.; MONTENEGRO, Marilia M.; ZANARDO, Evelin Aline; DIAS, Alexandre T.; ASSUNCAO, Nilson A.; KIM, Chong A.; KULIKOWSKI, Leslie D.Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case Presentation: We report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p- in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p- syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings' samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. Discussion: The sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p- phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p- syndrome, which will allow a better understanding of the genotype-phenotype correlations.
- Complex structural rearrangement features suggesting chromoanagenesis mechanism in a case of 1p36 deletion syndrome(2014) ZANARDO, Evelin Aline; PIAZZON, Flavia Balbo; DUTRA, Roberta Lelis; DIAS, Alexandre Torchio; MONTENEGRO, Marilia Moreira; NOVO-FILHO, Gil Monteiro; COSTA, Thais Virginia Moura Machado; NASCIMENTO, Amom Mendes; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciGenome rearrangements are caused by the erroneous repair of DNA double-strand breaks, leading to several alterations that result in loss or gain of the structural genomic of a dosage-sensitive genes. However, the mechanisms that promote the complexity of rearrangements of congenital or developmental defects in human disease are unclear. The investigation of complex genomic abnormalities could help to elucidate the mechanisms and causes for the formation and facilitate the understanding of congenital or developmental defects in human disease. We here report one case of a patient with atypical clinical features of the 1p36 syndrome and the use of cytogenomic techniques to characterize the genomic alterations. Analysis by multiplex ligation-dependent probe amplification and array revealed a complex rearrangement in the 1p36.3 region with deletions and duplication interspaced by normal sequences. We also suggest that chromoanagenesis could be a possible mechanism involved in the repair and stabilization of this rearrangement.
conferenceObject Molecular autopsy reveals clues for genetic basis of congenital valve defect(2019) MADIA, F. A. R.; DIAS, A. T.; ZANARDO, E. A.; DAMASCENO, J. G.; NASCIMENTO, A. M.; COSTA, T. V. M. M.; CHEHIMI, S. N.; NOVO-FILHO, G. M.; MONTENEGRO, M. M.; OLIVEIRA, Y. G.; FREITAS, A. B.; VIEIRA, L. L.; SCHULTZ, R.; GONCALVES, F. T.; FRIDMAN, C.; KIM, C. A.; KULIKOWSKI, L. D.- 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.
conferenceObject Investigating the CNVs in routine diagnostics using WES and array in Brazilian patients(2019) ZANARDO, E. A.; CHEHIMI, S. N.; MONTEIRO, F. P.; MADIA, F. A. R.; NOVO-FILHO, G. M.; DIAS, A. T.; MONTENEGRO, M. M.; OLIVEIRA, Y. G.; VIEIRA, L. L.; ROCHA, M.; BRASIL, A. S.; NASCIMENTO, A. M.; COSTA, T. V. M. M.; DAMASCENO, J. G.; KOK, F.; KIM, C. A.; KULIKOWSKI, L. D.- 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
conferenceObject Repetitive elements associated with breakpoints of distal 5p deletions suggest mechanisms mediating these rearrangements(2019) CHEHIMI, S. N.; ZANARDO, E. A.; MADIA, F. A. R.; DIAS, A. T.; NOVO-FILHO, G. M.; MONTENEGRO, M. M.; NASCIMENTO, A. M.; DAMASCENO, J. G.; OLIVEIRA, Y. G.; VIEIRA, L. L.; KIM, C. A.; KULIKOWSKI, L. D.- Application of Whole-Exome Sequencing in for updates Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations(2020) ZANARDO, Evelin A.; MONTEIRO, Fabiola P.; CHEHIMI, Samar N.; OLIVEIRA, Yanca G.; DIAS, Alexandre T.; COSTA, Larissa A.; RAMOS, Luiza L.; NOVO-FILHO, Gil M.; MONTENEGRO, Marilia M.; NASCIMENTO, Amom M.; KITAJIMA, Joao P.; KOK, Fernando; KULIKOWSKI, Leslie D.Overcoming challenges for the unambiguous detection of copy number variations is essential to broaden our understanding of the role of genomic variants in the clinical phenotype. With the improvement of software and databases, whole-exome sequencing quickly can become an excellent strategy in the routine diagnosis of patients with a developmental delay and/or multiple congenital malformations. However, even after a detailed analysis of pathogenic single-nucleotide variants and indels in known disease genes, using whole-exome sequencing, some patients with suspected syndromic conditions are left without a conclusive diagnosis. These negative results could be the result of different factors including nongenetic etiologies, lack of knowledge about the genes that cause different disease phenotypes, or, in some cases, a deletion or duplication of genomic information not routinely detectable by whole-exome sequencing variant calling. Although copy number variant detection is possible using whole-exome sequencing data, such analysis presents significant challenges and cannot yet be used to replace chromosomal arrays for identification of deletions or duplications.
- Post-mortem cytogenomic investigations in patients with congenital malformations(2016) DIAS, Alexandre Torchio; ZANARDO, Evelin Aline; DUTRA, Roberta Lelis; PIAZZON, Flavia Balbo; NOVO-FILHO, Gil Monteiro; MONTENEGRO, Marilia Moreira; NASCIMENTO, Amom Mendes; ROCHA, Mariana; MADIA, Fabricia Andreia Rosa; COSTA, Thais Virginia Moura Machado; MILANI, Cintia; SCHULTZ, Regina; GONCALVES, Fernanda Toledo; FRIDMAN, Cintia; YAMAMOTO, Guilherme Lopes; BERTOLA, Debora Romeo; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciCongenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), micro satellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin -embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p1132); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C > G (c.746C > G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.
conferenceObject Multi-gene panel testing improves diagnosis in Brazilian patients with Early-Onset Epilepsy(2019) NOVO FILHO, G. M.; DIAS, A. T.; NASCIMENTO, A. M.; DAMASCENO, J. G.; ZANARDO, E. A.; CHEHIMI, S. N.; MADIA, F. A. R.; AKL, O. S.; AKL, O. S.; MONTENEGRO, M. M.; OLIVEIRA, Y. G.; VIEIRA, L. L.; MANREZA, M. L. G.; KULIKOWSKI, L. D.
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