MARILIA MOREIRA MONTENEGRO
Projetos de Pesquisa
Unidades Organizacionais
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
33 resultados
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- 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.
- Cytogenomics Investigation of Infants with Congenital Heart Disease: Experience of a Brazilian Center(2022) GRASSI, Marcilia Sierro; MONTENEGRO, Marilia; ZANARDO, Evelin Aline; PASTORINO, Antonio Carlos; DORNA, Mayra Barros; KIM, Chong; JATENE, Marcelo; MIURA, Nana; KULIKOWSKI, Leslie; CARNEIRO-SAMPAIO, MagdaBackground: Some syndromes have specific and easily recognizable features, while others may be more complex to identify and may present different phenotypic manifestations, for example. An etiological diagnosis is important to understand the nature of the disease, to establish the prognosis and to start the treatment, allowing the inclusion of patients in society and reducing the financial cost of such diseases. Objective: The initial proposal of this study was cytogenetic screening for the detection of the 22q11.2 deletion syndrome in consecutive newborns and infants with congenital heart disease using the multiplex ligation-dependent probe amplification (MLPA) technique. Therefore, throughout our research, other genomic alterations were identified in these cardiac patients. Thus, our objective was extended to investigate these other cytogenetic alterations. Methods: We investigated 118 neonates with congenital heart diseases born consecutively during one year using the MLPA technique. Results: The MLPA technique allowed the detection of 22q11.2DS in 10/118 patients (8.5%). Other genomic alterations were also identified in 6/118 patients (5%): 1p36 del, 8p23 del (2 cases), 7q dup, 12 dup and 8q24 dup. Conclusion: This study highlights the relevance of detecting genomic alterations that are present in newborns and infants with congenital cardiac diseases using cytogenomic tools.
- 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.
- Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p-syndrome(2022) CHEHIMI, Samar Nasser; ALMEIDA, Vanessa Tavares; NASCIMENTO, Amom Mendes; ZANARDO, Evelin Aline; OLIVEIRA, Yanca Gasparini de; CARVALHO, Gleyson Francisco da Silva; WOLFF, Beatriz Martins; MONTENEGRO, Marilia Moreira; ASSUNCAO, Nilson Antonio de; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciObjectives: 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.
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.
- 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.
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.- Cytogenomic delineation and clinical follow-up of 10 Brazilian patients with Pallister-Killian syndrome(2015) COSTA, Larissa Sampaio de Athayde; ZANDONA-TEIXEIRA, Aline C.; MONTENEGRO, Marilia M.; DIAS, Alexandre T.; DUTRA, Roberta L.; HONJO, Rachel S.; BERTOLA, Debora R.; KULIKOWSKI, Leslie D.; KIM, Chong A.Background: Pallister-Killian syndrome (PKS) is a sporadic genetic disorder caused by the presence of a tissue-specific mosaicism for isochromosome 12p - i(12) (p10) and is characterized by facial dysmorphism including coarse facies, upslanting palpebral fissures, bitemporal alopecia, pigmentary skin anomalies, developmental delay, hypotonia and seizures. Although typical clinical features of PKS commonly exist, clinicians often do not raise the possibility of this diagnosis. Results: We reviewed the medical records of 10 patients with confirmed PKS followed in our service (since 1990 to 2015). Age at diagnosis varied from prenatal to 3 years and clinical features were consistent with those described in the literature. In all patients, peripheral blood karyotypes were normal and cytogenomic study was performed in order to confirm the diagnosis. Three of these patients had PKS diagnosis confirmed by buccal smear MLPA. Conclusion: An early conclusion from our results demonstrated that MLPA on buccal smears is a good and non-invasive method to detect extra copies of 12p and should be considered as the first exam, before a skin biopsy for a fibroblast karyotype is performed.
- Lymphoproliferative disorder with polyautoimmunity and hypogammaglobulinemia: An unusual presentation of 22q11.2 deletion syndrome(2020) SOARES, Diogo C.; DANTAS, Anelisa G.; MATTA, Marina C.; PASTORINO, Antonio C.; MELARAGNO, Maria Isabel; KULIKOWSKI, Leslie; MONTENEGRO, Marilia; KIM, Chong A.; CARNEIRO-SAMPAIO, Magda; TORRES, Leuridan C.22q11.2 deletion syndrome (22q11.2DS) has a heterogeneous presentation that includes multiple congenital anomalies and immunodeficiency, one of the most striking features. Usually, it is characterized by T cell lymphopenia, B cell dysfunction and autoimmunity. Here, we describe an unusual case of 22q11.2DS in a patient with lymphoproliferative disorder, polyautoimmunity and hypogammaglobulinemia.