SORAHIA DOMENICE
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
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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Agora exibindo 1 - 8 de 8
- 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.
- 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.
- 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.
- Disorders of sex development: effect of molecular diagnostics(2015) ACHERMANN, John C.; DOMENICE, Sorahia; BACHEGA, Tania A. S. S.; NISHI, Mirian Y.; MENDONCA, Berenice B.Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs.
- The Use of Genetics for Reaching a Diagnosis in XY DSD(2022) AHMED, S. Faisal; ALIMUSINA, Malika; BATISTA, Rafael L.; DOMENICE, Sorahia; GOMES, Nathalia Lisboa; MCGOWAN, Ruth; PATJAMONTRI, Supitcha; MENDONCA, Berenice B.Reaching a firm diagnosis is vital for the long-term management of a patient with a difference or disorder of sex development (DSD). This is especially the case in XY DSD where the diagnostic yield is particularly low. Molecular genetic technology is playing an increasingly important role in the diagnostic process, and it is highly likely that it will be used more often at an earlier stage in the diagnostic process. In many cases of DSD, the clinical utility of molecular genetics is unequivocally clear, but in many other cases there is a need for careful exploration of the benefit of genetic diagnosis through long-term monitoring of these cases. Furthermore, the incorporation of molecular genetics into the diagnostic process requires a careful appreciation of the strengths and weaknesses of the evolving technology, and the interpretation of the results requires a clear understanding of the wide range of conditions that are associated with DSD.
- Quality of life of patients with 46,XX and 46,XY disorders of sex development(2015) AMARAL, Rita Cassia; INACIO, Marlene; BRITO, Vinicius N.; BACHEGA, Tania A. S. S.; DOMENICE, Sorahia; ARNHOLD, Ivo J. P.; MADUREIRA, Guiomar; GOMES, Larissa; COSTA, Elaine M. F.; MENDONCA, Berenice B.Disorders of sex development (DSD) result from abnormalities in the complex process of sex determination and differentiation. An important consideration to guide the assignment of social sex in newborns with ambiguous genitalia is the quality of life (QoL) of these patients in adulthood. The rarity of most DSD conditions makes it difficult to conduct a long-term follow-up of affected patients through adulthood. This review of papers on the QoL of DSD patients evaluated in developing and developed countries by qualitative and quantitative instruments revealed a large spectrum of QoL, ranging from very poor to similar to, or even better than, the normal population. A more adequate QoL was found in patients from tertiary centres, indicating that the medical care of DSD patients should be multidisciplinary and carried out by specialized teams.
- 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.
- Androgen insensitivity syndrome: a review(2018) BATISTA, Rafael Loch; COSTA, Elaine M. Frade; RODRIGUES, Andresa de Santi; GOMES, Nathalia Lisboa; FARIA JR., Jose Antonio; NISHI, Mirian Y.; ARNHOLD, Ivo Jorge Prado; DOMENICE, Sorahia; MENDONCA, Berenice Bilharinho deAndrogenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46, XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.