ELISANGELA PEREIRA DE SOUZA QUEDAS
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing(2018) CARVALHO, Rafael A.; URTREMARI, Betsaida; JORGE, Alexander A. L.; SANTANA, Lucas S.; QUEDAS, Elisangela P. S.; SEKIYA, Tomoko; LONGUINI, Viviane C.; MONTENEGRO, Fabio L. M.; LERARIO, Antonio M.; TOLEDO, Sergio P. A.; MARX, Stephen J.; TOLEDO, Rodrigo A.; JR, Delmar M. LourencoBackground: Loss-of-function germline MEN1 gene mutations account for 75-95% of patients with multiple endocrine neoplasia type 1 (MEN1). It has been postulated that mutations in non-coding regions of MEN1 might occur in some of the remaining patients; however, this hypothesis has not yet been fully investigated. Objective: To sequence for the entire MEN1 including promoter, exons and introns in a large MEN1 cohort and determine the mutation profile. Methods and patients: A target next-generation sequencing (tNGS) assay comprising 7.2 kb of the full MEN1 was developed to investigate germline mutations in 76 unrelated MEN1 probands (49 familial, 27 sporadic). tNGS results were validated by Sanger sequencing (SS), and multiplex ligation-dependent probe amplification (MLPA) assay was applied when no mutations were identifiable by both tNGS and SS. Results: Germline MEN1 variants were verified in coding region and splicing sites of 57/76 patients (74%) by both tNGS and SS (100% reproducibility). Thirty-eight different pathogenic or likely pathogenic variants were identified, including 13 new and six recurrent variants. Three large deletions were detected by MLPA only. No mutation was detected in 16 patients. In untranslated, regulatory or in deep intronic MEN1 regions of the 76 MEN1 cases, no point or short indel pathogenic variants were found in untranslated, although 33 benign/likely benign and three new VUS variants were detected. Conclusions: Our study documents that point or short indel mutations in non-coding regions of MEN1 are very rare events. Also, tNGS proved to be a highly effective technology for routine genetic MEN1 testing.
- Genetic investigation of patients with tall stature(2020) ALBUQUERQUE, Edoarda Vasco de Albuquerque; FUNARI, Mariana Ferreira de Assis; QUEDAS, Elisangela Pereira de Souza; KAWAHIRA, Rachel Sayuri Honjo; JALLAD, Raquel Soares; HOMMA, Thais Kataoka; MARTIN, Regina Matsunaga; BRITO, Vinicius Nahime; MALAQUIAS, Alexsandra Christianne; LERARIO, Antonio Marcondes; ROSENBERG, Carla; KREPISCHI, Ana Cristina Victorino; KIM, Chong Ae; ARNHOLD, Ivo Jorge Prado; JORGE, Alexander Augusto de LimaContext: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.