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
99 resultados
Resultados de Busca
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bookPart Distúrbios do desenvolvimentos sexual(2017) DOMENICE, Sorahia; COSTA, Elaine Maria Frade; MENDONçA, Berenice Bilharinho deconferenceObject Inherited Digenic Missense Variants in FGFR2 and MAP3K1 Genes in Two Siblings with 46,XY Partial Gonadal Dysgenesis(2014) MACHADO, Aline Zamboni; NISHI, Mirian Yumie; COSTA, Elaine Maria Frade; MENDONCA, Berenice B.; DOMENICE, Sorahia- Discriminating between virilizing ovary tumors and ovary hyperthecosis in postmenopausal women: clinical data, hormonal profiles and image studies(2017) YANCE, V. R. V.; MARCONDES, J. A. M.; ROCHA, M. P.; BARCELLOS, C. R. G.; DANTAS, W. S.; AVILA, A. F. A.; BARONI, R. H.; CARVALHO, F. M.; HAYASHIDA, S. A. Y.; MENDONCA, B. B.; DOMENICE, S.Background: The presence of virilizing signs associated with high serum androgen levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized postmenopausal women. The differential diagnosis between these two conditions is often difficult. Objective: To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. Design: A retrospective study. Setting: A tertiary center. Main outcome measures: Clinical data, hormonal status (T, E2, LH and FSH), pelvic images (transvaginal sonography and MRI) and anatomopathology were reviewed. Patients: Thirty-four postmenopausal women with a diagnosis of VOT (13 women) and OH (21 women) were evaluated retrospectively. Results: Clinical signs of hyperandrogenism were more prevalent in the VOT group than the OH group. Although the VOT group showed higher T and E2 levels and lower gonadotropin levels than the OH group, a great overlap occurred among the hormone levels. A pelvic MRI provided an accurate differentiation of these two conditions. Conclusion: In this group of patients, the main features contributing to the differential diagnosis of VOT and OH were serum levels of testosterone and gonadotropins and the presence of an ovarian nodule identified on the MRI. Although the association of clinical, hormonal and radiological features contributes to the differential diagnosis of these two conditions, histopathological analysis remains the gold standard for the diagnosis of ovarian hyperandrogenism in postmenopausal women.
- 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.
- Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy(2015) CUNHA, F. S.; DOMENICE, S.; CAMARA, V. L.; SIRCILI, M. H. P.; GOOREN, L. J. G.; MENDONCA, B. B.; COSTA, E. M. F.Male-to-female transsexual persons use oestrogens+antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-adminstration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23years and another one in a 42year old who had initiated oestrogen treatment at the age of 17years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.
- Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency(2020) FRANCA, Monica M.; FUNARI, Mariana F. A.; LERARIO, Antonio M.; SANTOS, Mariza G.; NISHI, Mirian Y.; DOMENICE, Sorahia; MORAES, Daniela R.; COSTALONGA, Everlayny F.; MACIEL, Gustavo A. R.; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; MENDONCA, Berenice B.Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities.
- 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.
bookPart Biologia molecular dos tumores endócrinos(2013) LERARIO, Antonio Marcondes; FRAGOSO, Maria Candida Barisson; BRITO, Luciana Pinto; MARTIN, Regina Matsunaga; TRARBACH, Erika Barbosa; MARUI, Suemi; TOLEDO, Rodrigo de Almeida; DOMENICE, Sorahia; MENDONçA, Berenice Bilharinho de- 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.
- Homozygous Inactivating Mutation in NANOS3 in Two Sisters with Primary Ovarian Insufficiency(2014) SANTOS, Mariza G.; MACHADO, Aline Z.; MARTINS, Conceicao N.; DOMENICE, Sorahia; COSTA, Elaine M. F.; NISHI, Mirian Y.; FERRAZ-DE-SOUZA, Bruno; JORGE, Soraia A. C.; PEREIRA, Carlos A.; SOARDI, Fernanda C.; MELLO, Maricilda P. de; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; MENDONCA, Berenice B.Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lysmutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.