NATHALIA LISBOA ROSA ALMEIDA GOMES
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
33 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 33
- Disorders of Sex Development-Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation(2020) GOMES, Nathalia Lisboa; CHETTY, Tarini; JORGENSEN, Anne; MITCHELL, Rod T.Disorders (or differences) of sex development (DSD) are a heterogeneous group of congenital conditions with variations in chromosomal, gonadal, or anatomical sex. Impaired gonadal development is central to the pathogenesis of the majority of DSDs and therefore a clear understanding of gonadal development is essential to comprehend the impacts of these disorders on the individual, including impacts on future fertility. Gonadal development was traditionally considered to involve a primary 'male' pathway leading to testicular development as a result of expression of a small number of key testis-determining genes. However, it is increasingly recognized that there are several gene networks involved in the development of the bipotential gonad towards either a testicular or ovarian fate. This includes genes that act antagonistically to regulate gonadal development. This review will highlight some of the novel regulators of gonadal development and how the identification of these has enhanced understanding of gonadal development and the pathogenesis of DSD. We will also describe the impact of DSDs on fertility and options for fertility preservation in this context.
- 46,XY disorder of sex development (DSD) due to 17 beta-hydroxysteroid dehydrogenase type 3 deficiency(2017) MENDONCA, Berenice B.; GOMES, Nathalia Lisboa; COSTA, Elaine M. F.; INACIO, Marlene; MARTIN, Regina M.; NISHI, Mirian Y.; CARVALHO, Filomena Marino; TIBOR, Francisco Denes; DOMENICE, Sorahia17 beta-hydroxysteroid dehydrogenase 3 deficiency consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. External genitalia range from female-like to atypical genitalia and most affected males are raised as females. Virilization in subjects with 17 beta-HSD3 deficiency occurs at the time of puberty and several of them change to male social sex. In male social sex patients, testes can be safely maintained, as long as they are positioned inside the scrotum The phenotype of 46,XY DSD due to 17 beta-HSD3 deficiency is extremely variable and clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5 alpha-reductase 2 deficiency. Laboratory diagnosis is based on a low testosterone/androstenedione ratio due to high serum levels of androstenedione and low levels of testosterone. The disorder is caused by a homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17 beta-HSD3 isoenzyme leading to an impairment of the conversion of 17-keto into 17-hydroxysteroids. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review-the previously reported cases of 17 beta-HSD3 deficiency adding our own cases. (C) 2016 Published by Elsevier Ltd.
- 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
- 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.
- Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development(2023) JR, Jose Antonio Diniz Faria; MORAES, Daniela R.; KULIKOWSKI, Leslie Domenici; BATISTA, Rafael Loch; GOMES, Nathalia Lisboa; NISHI, Mirian Yumie; ZANARDO, Evelin; NONAKA, Carolina Kymie Vasques; SOUZA, Bruno Solano de Freitas; MENDONCA, Berenice Bilharinho; DOMENICE, SorahiaBackground: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. Results: In two patients, the diagnosis of 46,XX SRY + DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. Conclusions: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD.
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, Ajay- 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 de