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
35 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 35
- Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor(2018) BATISTA, Rafael Loch; RODRIGUES, Andresa De Santi; MACHADO, Aline Zamboni; NISHI, Mirian Yumie; CUNHA, Flavia Siqueira; SILVA, Rosana Barbosa; COSTA, Elaine M. F.; MENDONCA, Berenice B.; DOMENICE, SorahiaBackground: Androgen insensitivity syndrome (AIS) is the most frequent etiology of 46, XY disorders of sex development (DSDs), and it is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. AIS patients present a broad phenotypic spectrum and individuals with a partial phenotype present with different degrees of undervirilized external genitalia. There are more than 500 different AR gene allelic variants reported to be linked to AIS, but the presence of somatic mosaicisms has been rarely identified. In the presence of a wild-type AR gene, a significant degree of spontaneous virilization at puberty can be observed, and it could influence the gender assignment, genetic counseling and the clinical and psychological management of these patients and the psychosexual outcomes of these patients are not known. Case presentation: In this study, we report two patients with AR allelic variants in heterozygous (c.382G>T and c.1769-1G>C) causing a partial AIS (PAIS) phenotype. The first patient was raised as female and she had undergone a gonadectomy at puberty. In both patients there was congruency between gender of rearing and gender identity and gender role. Conclusions: Somatic mosaicism is rare in AIS and nonsense AR variant allelic can cause partial AIS phenotype in this situation. Despite the risk of virilization and prenatal androgen exposure, the gender identity and gender role was concordant with sex of rearing in both cases. A better testosterone response can be expected in male individuals and this should be considered in the clinical management.
- Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life(2019) WISNIEWSKI, Amy B.; BATISTA, Rafael L.; COSTA, Elaine M. F.; FINLAYSON, Courtney; SIRCILI, Maria Helena Palma; DENES, Francisco Tibor; DOMENICE, Sorahia; MENDONCA, Berenice B.Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. Advances in the clinical care of patients and families affected by 46,XY DSD have been achieved since publication of the original Consensusmeeting in 2006. The aims of this paper are to review what is known about morbidity and mortality, diagnostic tools and timing, sex of rearing, endocrine and surgical treatment, fertility and sexual function, and quality of life in people with 46,XY DSD. The role for interdisciplinary health care teams, importance of establishing a molecular diagnosis, and need for research collaborations using patient registries to better understand long-term outcomes of specific medical and surgical interventions are acknowledged and accepted. Topics that require further study include prevalence and incidence, understanding morbidity and mortality as these relate to specific etiologies underlying 46,XY DSD, appropriate and optimal options for genitoplasty, long-term quality of life, sexual function, involvement with intimate partners, and optimizing fertility potential.
- Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with Partial Androgen Insensitivity Syndrome in an Individual with 47, XXY Karyotype(2017) BATISTA, Rafael L.; RODRIGUES, Andresa S.; NISHI, Mirian Y.; FEITOSA, Alina C. R.; GOMES, Nathalia L. R. A.; JUNIOR, Jose Antonio F.; DOMENICE, Sorahia; COSTA, Elaine M. F.; MENDONCA, Berenice B. deThere are only 2 patients with 47, XXY karyotype and androgen receptor (AR) gene mutation reported in the literature, and both are diagnosed as complete androgen insensitivity syndrome (CAIS). We report a 22-year-old female with 47, XXY karyotype and atypical external genitalia. Sequencing of AR revealed the heterozygous p.Asn849Lys*32 mutation, and extensive X chromosome microsatellite analysis showed homozygosity for Xp and heterozygosity for Xq, suggesting partial X maternal isodisomy. Partial androgen insensitivity syndrome (PAIS) developed in this case, probably because of the presence of the heterozygous AR mutation and random X-inactivation of the healthy allele. This is the first report of a female patient with 47, XXY karyotype and PAIS phenotype. (C) 2017 S.Karger AG, Basel
conferenceObject DEAH-Box Helicase 37defects (DXH37) Defects Are a Novel Cause of 46,XY Gonadal Dysgenesis(2018) GOMES, Nathalia; SILVA, Thatiana; LERARIO, Antonio; BATISTA, Rafael Loch; FARIA JUNIOR, Jose Antonio; MORAES, Daniela; COSTA, Elaine Maria Frade; NISHI, Mirian; CARVALHO, Luciani Renata; FORCLAZ, Maria Veronica; PAPAZIAN, Regina; MARTINEZ-AGUAYO, Alejandro; PAULA, Leila Pedroso de; CARVALHO, Filomena Marino; VILAIN, Erick; BARSEGHYAN, Hayk Barseghyan; KEEGAN, Catherine; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoconferenceObject 46,XY Partial gonadal dysgenesis; diagnosis and long-term outcome at puberty(2022) CUCCARO, Rieko Tadokoro; HUGHES, Ieuan; COOLS, Martine; VIJVER, Koen van de; MENDONCA, Berenice Bilharinho de; DOMENICE, Sorahia; BATISTA, Rafael L.; DALLAGO, Renata Thomazini; GOMES, Nathalia Lisboa; COSTA, Elaine F.; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; ANDRADE, Juliana Gabriel Ribeiro de; LUCAS-HERALD, Angela; BRYCE, Jillian; HANNEMA, Sabine; JUUL, Anders; GLOBA, Eugenia; ELREAVEY, Kenneth M.; BARONIO, Federico; DACAL, Jimena Lopez; DARENDELILER, Feyza; POYRAZOGLU, Sukran; KOLESINSKA, Zofia; NIEDZIELA, Marek; CLAAHSEN, Hedi; AKKER, Erica L. T. van den; HERRMANN, Gloria; ATAPATTU, Navoda; JAIN, Vandana; SHARMA, Rajni; BETTERDORF, Markus; KONRAD, Daniel; HOLTERHUS, Paul Martin; FICA, Simona; SKAE, Mars; RUSSO, Gianni; STANCAMPIANO, Marianna Rita; GAZDAGH, Gabriella; DAVIES, Justin H.; MOHAMED, Zainaba; SENEVIRATNE, Sumudu Nimali; GURAN, Tulay; GUVEN, Ayla; WASNIEWSKA, Malgorzata; MLADENOV, Vilhelm; VERKAUSKAS, Gilvydas; MARKOSYAN, Renata; KORBONITS, Marta; HIORT, Olaf; WAGNER, IsabelViola; AHMED, S. Faisal; THANKAMONY, AjayconferenceObject 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.
conferenceObject Gonadal morphology in 46,XY gonadal dysgenesis: I-DSD Registry-based study(2022) TADOKORO-CUCCARO, Rieko; HUGHES, Ieuan; COOLS, Martine; VIJVER, Koen van de; MENDONCA, Berenice Bilharinho de; DOMENICE, Sorahia; BATISTA, Rafael L.; DALLAGO, Renata Thomazini; GOMES, Nathalia Lisboa; COSTA, Elaine F.; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; ANDRADE, Juliana Gabriel Ribeiro de; LUCAS-HERALD, Angela; BRYCE, Jillian; HANNEMA, Sabine; JUUL, Anders; GLOBA, Eugenia; ELREAVEY, Kenneth M.; BARONIO, Federico; DACAL, Jimena Lopez; DARENDELILER, Feyza; POYRAZOGLU, Sukran; KOLESINSKA, Zofia; NIEDZIELA, Marek; GRINTEN, Hedi L. Claahsen-van der; AKKE, Erica L. T. van den; HERRMANN, Gloria; ATAPATTU, Navoda; JAIN, Vandana; SHARMA, Rajni; BETTENDORF, Markus; KONRAD, Daniel; HOLTERHUS, Paul Martin; FICA, Simona; SKAE, Mars; RUSSO, Gianni; STANCAMPIANO, Marianna Rita; GAZDAGH, Gabriella; DAVIES, Justin H.; MOHAMED, Zainaba; SENEVIRATNE, Sumudu Nimali; GURAN, Tulay; GUVEN, Ayla; WASNIEWSKA, Malgorzata; MLADENOV, Vilhelm; VERKAUSKAS, Gilvydas; MARKOSYAN, Renata; KORBONITS, Marta; AHMED, S. Faisal; HIORT, Olaf; WAGNER, Isabel; THANKAMONY, AjayconferenceObject 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 deconferenceObject Final adult height in SRY-negative 46, XX ovotesticular differences of sex development individuals(2019) FERRARI, Maria Tereza Martins; RODRIGUES, Daniela Moraes; GOMES, Nathalia Lisboa; NISHI, Mirian Yumi; BATISTA, Rafael Loch; COSTA, Elaine Maria Frade; MENDONCA, Berenice Bilharinho; DOMENICE, Sorahia; CRUZ, Patricia Sales Marques; SIRCILI, Maria Helena