BARBARA LEITAO BRAGA
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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conferenceObject Low Frequency of Pathogenic Allelic Variants in the 46,XY Differences of Sex Development (DSD)-Related Genes in Small for Gestational Age Children with Hypospadias(2019) BRAGA, B. L.; GOMES, L. N.; NISHI, M. Y.; FREIRE, B. L.; BATISTA, R. L.; FUNARI, M. F. A.; COSTA, E. M. F.; LERARIO, A. M.; DOMENICE, S.; JUNIOR, J. A. D. F.; JORGE, A. A. L.; MENDONCA, B. B.- Variants in 46,XY DSD-Related Genes in Syndromic and Non-Syndromic Small for Gestational Age Children with Hypospadias(2022) BRAGA, B. L.; GOMES, N. L.; NISHI, M. Y.; FREIRE, B. L.; BATISTA, R. L.; FARIA JUNIOR, J. A. D.; FUNARI, M. F. A.; BENEDETTI, A. F. F.; NARCIZO, A. De Moraes; CARDOSO, L. Cavalca; LERARIO, A. M.; GUERRA-JUNIOR, G.; COSTA, E. M. F.; DOMENICE, S.; JORGE, A. A. L.; MENDONCA, B. B.Hypospadias is a common congenital disorder of male genital formation. Children born small for gestational age (SGA) present a high frequency of hypospadias of undetermined etiology. No previous study investigated the molecular etiology of hypospadias in boys born SGA using massively parallel sequencing. Our objective is to report the genetic findings of a cohort of patients born SGA with medium or proximal hypospadias. We identified 46 individuals with this phenotype from a large cohort of 46,XY DSD patients, including 5 individuals with syndromic features. DNA samples from subjects were studied by either whole exome sequencing or target gene panel approach. Three of the syndromic patients have 5 main clinical features of Silver-Russell syndrome (SRS) and were first studied by MLPA. Among the syndromic patients, loss of DNA methylation at the imprinting control region H19/IGF2 was identified in 2 individuals with SRS clinical diagnosis. Two novel pathogenic variants in compound heterozygous state were identified in the CUL7 gene establishing the diagnosis of 3M syndrome in one patient, and a novel homozygous variant in TRIM37 was identified in another boy with Mulibrey nanism phenotype. Among the non-syndromic subjects, 7 rare heterozygous variants were identified in 6 DSD-related genes. However, none of the variants found can explain the phenotype by themselves. In conclusion, a genetic defect that clarifies the etiology of hypospadias was not found in most of the non-syndromic SGA children, supporting the hypothesis that multifactorial causes, new genes, and/or unidentified epigenetic defects may have an influence in this condition.
- 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.