ELAINE MARIA FRADE COSTA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, 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
11 resultados
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- Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals(2016) DOMENICE, Sorahia; MACHADO, Aline Zamboni; FERREIRA, Frederico Moraes; FERRAZ-DE-SOUZA, Bruno; LERARIO, Antonio Marcondes; LIN, Lin; NISHI, Mirian Yumie; GOMES, Nathalia Lisboa; SILVA, Thatiana Evelin da; SILVA, Rosana Barbosa; CORREA, Rafaela Vieira; MONTENEGRO, Luciana Ribeiro; NARCISO, Amanda; COSTA, Elaine Maria Frade; ACHERMANN, John C.; MENDONCA, Berenice BilharinhoSteroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Mullerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309-320, 2016. (c) 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.
conferenceObject Sexual Outcomes in Brazilian Patients with 46,XY DSD(2016) BATISTA, Rafael Loch; INACIO, Marlene; CUNHA, Flavia Siqueira; GOMES, Nathalia Lisboa; BRITO, Vinicius Nahime; COSTA, Elaine Frade; DOMENICO, Sorahia; MENDONCA, Berenice Bilharinho debookPart Distúbios do Desenvolvimento Sexual(2016) COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONçA, Berenice Bilharinho deconferenceObject Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Accordingly Gender Assignment(2016) GOMES, Nathalia; COSTA, Elaine; ZAMBONI, Aline; NISHI, Mirian; BATISTA, Rafael; CUNHA, Flavia; INACIO, Marlene; DOMENICE, Sorahia; MENDONCA, BereniceconferenceObject Final Adult Height of Patients with Disorders of Sex Development (DSD) Associated with Sex Chromosome Abnormalities 45,X/46,XY or 45,X/46,X,+Y Variants(2016) FARIA JUNIOR, J. A. D.; GOMES, N. L.; BATISTA, R. L.; MORAES, D. R.; SCALCO, R.; NISHI, M. Y.; JORGE, A. A. L.; ULTRA, M. A. M. S.; COSTA, E. M. F.; MENDONCA, B. B.; DOMENICE, S.conferenceObject Exonic Splicing Mutations by Silent Nucleotide Variation in the Androgen Receptor Gene Causes Androgen Insensitivity Syndrome(2016) BATISTA, Rafael Loch; RODRIGUES, Andreza de Santi; SILVA, Tathiana Evilen da; CUNHA, Flavia Siqueira; GOMES, Nathalia Lisboa; RODRIGUES, Daniela; DOMENICE, Sorahia; COSTA, Elaine Frade; MENDONCA, Berenice Bilharinho de- Steroid 5 alpha-reductase 2 deficiency(2016) MENDONCA, Berenice B.; BATISTA, Rafael Loch; DOMENICE, Sorahia; COSTA, Elaine M. F.; ARNHOLD, Ivo J. P.; RUSSELL, David W.; WILSON, Jean D.Dihydrotestosterone is a potent androgen metabolite formed from testosterone by action of 5 alpha-reductase isoenzymes. Mutations in the type 2 isoenzyme cause a disorder of 46,XY sex development, termed 5a-reductase type 2 deficiency and that was described forty years ago. Many mutations in the encoding gene have been reported in different ethnic groups. In affected 46,XY individuals, female external genitalia are common, but Mullerian ducts regress, and the internal urogenital tract is male. Most affected males are raised as females, but virilization occurs at puberty, and male social sex develops thereafter with high frequency. Fertility can be achieved in some affected males with assisted reproduction techniques, and adults with male social sex report a more satisfactory sex life and quality of life as compared to affected individuals with female social sex.
conferenceObject Molecular Analysis of Androgen Receptor Gene in a Cohort of Brazilian Patients with Androgen Insensitivity Syndrome(2016) BATISTA, R. L.; ANDRESA, D. S. R.; ARNHOLD, I. J. P.; CUNHA, F. S.; LISBOA, N. G.; FARIA JUNIOR, J. A. D.; COSTA, E. M. F.; DOMENICE, S.; MENDONCA, B. B.- Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects(2016) CARVALHO, Luciane Carneiro de; BRITO, Vinicius Nahime; MARTIN, Regina Matsunaga; ZAMBONI, Aline Machado; GOMES, Larissa Garcia; INACIO, Marlene; MERMEJO, Livia Mara; COELI-LACCHINI, Fernanda; TEIXEIRA, Virginia Ribeiro; GONCALVES, Fabricia Torres; CARRILHO, Alexandre Jose Faria; CAMARGO, Kenny Yelena Del Toro; FINKIELSTAIN, Gabriela Paula; TABOADA, Giselle Fernandes; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoObjective: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Design: Retrospective study. Setting: Tertiary care center. Patient(s): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. Intervention(s): None. Main Outcome Measure(s): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Result(s): Seventy-one percent of patients presented with primary amenorrhea, 500/0 had no breast development, and pubic hair was absent or sparse in all patients; 880/o had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.70/0 and ovarian macrocysts in 62.50/0 of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/ p.1223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Conclusion (s): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogoriadisiri point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. (Fertil Steil(R) 2016;105:1612-9. (C) 2016 by American Society for Reproductive Medicine.)
conferenceObject Targeted Massively Parallel Sequencing for the Molecular Diagnosis of 46, XY Disorders of Sex Development (DSD)(2016) GOMES, N. L.; LERARIO, A. M.; FRANCA, M. M.; NISHI, M. Y.; FUNARI, M. F.; COSTA, E. M. F.; FARIA JUNIOR, J. A. D.; BATISTA, R. L.; DOMENICE, S.; MENDONCA, B. B.