LUCIANA RIBEIRO MONTENEGRO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject X-Linked Central Precocious Puberty Associated with MECP2 defects(2022) CANTON, Ana; TINANO, Flavia; GUASTI, Leonardo; MONTENEGRO, Luciana; RYAN, Fiona; SHEARS, Deborah; MELO, Maria Edna; GOMES, Larissa; PIANA, Mariana; BRAUNER, Raja; ESPINO, Rafael; ESCRIBANO-MUNOZ, Arancha; PAGANONI, Alyssa; KORBONITS, Marta; SERAPHIM, Carlos Eduardo; FARIA, Aline; COSTA, Silvia; KREPISCHI, Ana Cristina; JORGE, Alexander; DAVID, Alessia; ARGENTE, Jesus; MENDONCA, Berenice; BRITO, Vinicius; HOWARD, Sasha; LATRONICO, Ana Claudia- High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort(2022) CRESPO, Raiane P.; ROCHA, Thais P.; MONTENEGRO, Luciana R.; NISHI, Mirian Y.; JORGE, Alexander A. L.; MACIEL, Gustavo A. R.; BARACAT, Edmund; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; GOMES, Larissa G.Context: Polycystic ovary syndrome (PCOS) etiology remains to be elucidated, but familial clustering and twin studies have shown a strong heritable component. Objective: The purpose of this study was to identify rare genetic variants that are associated with the etiology of PCOS in a preselected cohort. Methods: This prospective study was conducted among a selected group of women with PCOS. The study's inclusion criteria were patients with PCOS diagnosed by the Rotterdam criteria with the following phenotypes: severe insulin resistance (IR), normoandrogenic-normometabolic phenotype, adrenal hyperandrogenism, primary amenorrhea, and familial PCOS. Forty-five patients were studied by target sequencing, while 8 familial cases were studied by whole exome sequencing. Results: Patients were grouped according to the inclusion criteria with the following distribution: 22 (41.5%) with severe IR, 13 (24.5%) with adrenal hyperandrogenism, 7 (13.2%) with normoandrogenic phenotype, 3 (5.7%) with primary amenorrhea, and 8 (15.1%) familial cases. DNA sequencing analysis identified 1 pathogenic variant in LMNA, 3 likely pathogenic variants in INSR, PIK3R1, and DLK1, and 6 variants of uncertain significance level with interesting biologic rationale in 5 genes (LMNA, GATA4, NR5A1, BMP15, and FSHR). LMNA was the most prevalent affected gene in this cohort (3 variants). Conclusion: Several rare variants in genes related to IR were identified in women with PCOS. Although IR is a common feature of PCOS, patients with extreme or atypical phenotype should be carefully evaluated to rule out monogenic conditions.
- Targeted massively parallel sequencing panel to diagnose genetic endocrine disorders in a tertiary hospital(2022) NARCIZO, Amanda M.; CARDOSO, Lais C.; BENEDETTI, Anna F. F.; JORGE, Alexander A. L.; FUNARI, Mariana F. A.; BRAGA, Barbara L.; FRANCA, Monica M.; MONTENEGRO, Luciana R.; LERARIO, Antonio M.; NISHI, Mirian Y.; MENDONCA, Berenice B.Objectives: To analyze the efficiency of a multigenic targeted massively parallel sequencing panel related to endo-crine disorders for molecular diagnosis of patients assisted in a tertiary hospital involved in the training of medi-cal faculty.Material and methods: Retrospective analysis of the clinical diagnosis and genotype obtained from 272 patients in the Endocrine unit of a tertiary hospital was performed using a custom panel designed with 653 genes, most of them already associated with the phenotype (OMIM) and some candidate genes that englobes developmental, metabolic and adrenal diseases. The enriched DNA libraries were sequenced in NextSeq 500. Variants found were then classified according to ACMG/AMP criteria, with Varsome and InterVar.Results: Three runs were performed; the mean coverage depth of the targeted regions in panel sequencing data was 249x, with at least 96.3% of the sequenced bases being covered more than 20-fold. The authors identified 66 LP/P variants (24%) and 27 VUS (10%). Considering the solved cases, 49 have developmental dis-eases, 12 have metabolic and 5 have adrenal diseases.Conclusion: The application of a multigenic panel aids the training of medical faculty in an academic hospital by showing the picture of the molecular pathways behind each disorder. This may be particularly helpful in develop-mental disease cases. A precise genetic etiology provides an improvement in understanding the disease, guides decisions about prevention or treatment, and allows genetic counseling.
conferenceObject Usefulness of Next Generation Sequencing in the Molecular Diagnosis of McCune-Albright Syndrome in Peripheral Blood(2022) FARIA, Aline Guimaraes; JORGE, Alexander Augusto Lima; MONTENEGRO, Luciana; CANTO, Ana Pinheiro Machado; SERAPHIM, Carlos Eduardo; TINANO, Flavia Rezende; JALLAD, Raquel Soares; MARTIN, Regina Matsunaga; FRAGOSO, Maria Candida Villares; PINTO, Nadja Christina Souza; MENDONCA, Berenice Bilharinho; LATRONICO, Ana Claudia; BRITO, Vinicius Nahime- Contribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development(2022) GOMES, Nathalia Lisboa; BATISTA, Rafael Loch; NISHI, Mirian Y.; LERARIO, Antonio Marcondes; SILVA, Thatiana E.; NARCIZO, Amanda de Moraes; BENEDETTI, Anna Flavia Figueredo; FUNARI, Mariana Ferreira de Assis; FARIA JUNIOR, Jose Antonio; MORAES, Daniela Rodrigues; QUINTAO, Lia Mesquita Lousada; MONTENEGRO, Luciana Ribeiro; FERRARI, Maria Teresa Martins; JORGE, Alexander A.; ARNHOLD, Ivo J. P.; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoContext Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD). Objective To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients. Design/patients 209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS. Results Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively. Conclusions The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.