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
8 resultados
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- DSD Due to 5 alpha-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome(2012) COSTA, Elaine M. F.; DOMENICE, Sorahia; SIRCILI, Maria Helena; INACIO, Marlene; MENDONCA, Berenice B.Most of the patients with 5 alpha-RD 2 deficiency are reared in the female social sex due to their severely undervirilized external genitalia but similar to 60% who have not been submitted to orchiectomy in childhood undergo male social sex change at puberty. In our cohort of 30 cases from 18 families, all subjects were registered in the female social sex except for two children-one who had an affected uncle and the other who was diagnosed before being registered. The majority of the patients were satisfied with the long-term results of their treatment and surprisingly, penile length was not associated with satisfactory or unsatisfactory sexual activity. Steroid 5 alpha-RD2 deficiency should be included in the differential diagnosis of all newborns with 46,XY DSD with normal testosterone production before gender assignment or any surgical intervention because these patients should be considered males at birth.
- 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.
- 46,XY DSD due to 17 beta-HSD3 Deficiency and 5 alpha-Reductase Type 2 Deficiency(2011) INACIO, Marlene; SIRCILI, Maria Helena P.; BRITO, Vinicius N.; DOMENICE, Sorahia; OLIVEIRA-JUNIOR, Ari Alves; ARNHOLD, Ivo J. P.; TIBOR, Francisco D.; COSTA, Elaine M. F.; MENDONCA, Berenice B.
- Steroid 5 alpha-reductase 2 deficiency (Reprinted from vol 163, pg 206-211, 2016)(2017) 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 5 alpha-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. (C) 2016 Published by Elsevier Ltd.
- 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.
- Contribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development(2022) GOMES, Nathalia Lisboa; BATISTA, Rafael Loch; NISHI, Mirian Y.; LERARIO, Antonio Marcondes; SILVA, Thatiana E.; NARCIZO, Amanda de Moraes; BENEDETTI, Anna Flavia Figueredo; FUNARI, Mariana Ferreira de Assis; FARIA JUNIOR, Jose Antonio; MORAES, Daniela Rodrigues; QUINTAO, Lia Mesquita Lousada; MONTENEGRO, Luciana Ribeiro; FERRARI, Maria Teresa Martins; JORGE, Alexander A.; ARNHOLD, Ivo J. P.; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoContext Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD). Objective To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients. Design/patients 209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS. Results Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively. Conclusions The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.
- Psychosexual Aspects, Effects of Prenatal Androgen Exposure, and Gender Change in 46,XY Disorders of Sex Development(2019) BATISTA, Rafael Loch; INACIO, Marlene; ARNHOLD, Ivo Jorge Prado; GOMES, Nathalia Lisboa; FARIA JR., Jose Antonio Diniz; MORAES, Daniela Rodrigues de; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoContext: In 46,XY disorders of sexual development (DSD) patients, several factors may affect psychosexual development, leading to gender identity discrepancy and gender change later in life. Prenatal sexual steroid exposure and external genital virilization are considered to influence human psychosexual development, but their roles not completely understood yet. Design: A total of 144 individuals (18 to 60 years of age) with a clinical/molecular diagnosis of 46,XY DSD from a single tertiary center were enrolled. Psychosexual outcomes (gender role, gender identity, and sexual orientation) were assessed using questionnaires and psychological test. The Sinnecker score was used for genital virilization measurement. Prenatal androgen exposure was estimated according to 46,XY DSD etiology. Results: We found a positive association between prenatal androgen exposure and male psychosexual outcomes. Alternatively, prenatal estrogen exposure, age of gonadectomy, and the degree of external genital virilization did not influence any psychosexual outcome. There were 19% (n = 27) with gender change, which was associated with prenatal androgen exposure (P < 0.001) but not with the external genital virilization. The median age of gender change was 15 years, but most of the patients reported the desire for gender change earlier. Conclusions: Prenatal androgen exposure influenced psychosexual development in 46,XY DSD favoring male psychosexuality in all psychosexual outcomes, whereas the degree of external genital virilization did not influence these outcomes. The organizational effect of sexual steroids on psychosexuality at puberty appears to be weak in comparison with the prenatal effects. Prenatal androgen exposure also influenced female-to-male gender change frequency. All 46,XY DSD conditions with prenatal androgen exposure must be followed for gender issues in their management.
- Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency(2015) KHATTAB, Ahmed; YUEN, Tony; YAU, Mabel; DOMENICE, Sorahia; COSTA, Elaine Maria Frade; DIYA, Kazmi; MUHURI, Dwaipayan; PINA, Christian Enrique; NISHI, Mirian Yumie; YANG, Amy C.; MENDONCA, Berenice Biharinho de; NEW, Maria I.Steroid 17 beta-hydroxysteroid dehydrogenase III (17 beta-HSD3) deficiency is a rare autosomal recessive disorder that usually presents in patients with a 46, XY karyotype with ambiguous genitalia at birth. The 17 beta-HSD3 enzyme, which is encoded by the HSD17B3 gene, converts gonadal delta-4 androstenedione (Delta 4) to testosterone (T). Such 17 beta-HSD3 enzyme deficiency is expected to lead to an increased ratio of D4 to T when the patient undergoes a human chorionic gonadotropin stimulation (hCG) test. Two patients with 46, XY disorders of sexual differentiation were studied. Serum D4 and T levels were measured by HPLC tandem mass spectrometry. As one of the patients was born to consanguineous parents, we performed single nucleotide polymorphism (SNP) microarray to analyze regions of homozygosity (ROH). The HSD17B3 gene was sequenced using the Sanger method. Contrary to expectations, both patients demonstrated decreased D4/T ratio after hCG stimulation. Initial sequencing results for the androgen receptor or 5 alpha-reductase were negative for mutations. ROH analysis identified HSD17B3 as a candidate gene that might cause the disease. Sanger sequencing of the HSD17B3 gene confirmed 17 beta-HSD3 deficiency in both patients. Serum D4/T ratios are not reliable parameters for the diagnosis of 17 beta-HSD3 deficiency. Molecular genetic analysis provides accurate diagnosis.