MIRIAN YUMIE NISHI
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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.
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 Bilharinho- The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)(2018) CAVALCANTE, Isadora P.; NISHI, Mirian; ZERBINI, Maria Claudia N.; ALMEIDA, Madson Q.; BRONDANI, Vania B.; BOTELHO, Maria Luiza Anhaia de Arruda; TANNO, Fabio Y.; SROUGI, Victor; CHAMBO, Jose Luis; MENDONCA, Berenice B.; BERTHERAT, Jerome; LOTFI, Claudimara F. P.; FRAGOSO, Maria Candida B. V.The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.
- Identification of the first homozygous 1-bp deletion in GDF9 gene leading to primary ovarian insufficiency by using targeted massively parallel sequencing(2018) FRANCA, M. M.; FUNARI, M. F. A.; NISHI, M. Y.; NARCIZO, A. M.; DOMENICE, S.; COSTA, E. M. F.; LERARIO, A. M.; MENDONCA, B. B.Targeted massively parallel sequencing (TMPS) has been used in genetic diagnosis for Mendelian disorders. In the past few years, the TMPS has identified new and already described genes associated with primary ovarian insufficiency (POI) phenotype. Here, we performed a targeted gene sequencing to find a genetic diagnosis in idiopathic cases of Brazilian POI cohort. A custom SureSelect(XT) DNA target enrichment panel was designed and the sequencing was performed on Illumina NextSeq sequencer. We identified 1 homozygous 1-bp deletion variant (c.783delC) in the GDF9 gene in 1 patient with POI. The variant was confirmed and segregated using Sanger sequencing. The c.783delC GDF9 variant changed an amino acid creating a premature termination codon (p.Ser262Hisfs*2). This variant was not present in all public databases (ExAC/gnomAD, NHLBI/EVS and 1000Genomes). Moreover, it was absent in 400 alleles from fertile Brazilian women screened by Sanger sequencing. The patient's mother and her unaffected sister carried the c.783delC variant in a heterozygous state, as expected for an autosomal recessive inheritance. Here, the TMPS identified the first homozygous 1-bp deletion variant in GDF9. This finding reveals a novel inheritance pattern of pathogenic variant in GDF9 associated with POI, thus improving the genetic diagnosis of this disorder.
- Long-term outcomes and molecular analysis of a large cohort of patients with 46,XY disorder of sex development due to partial gonadal dysgenesis(2018) GOMES, Nathalia L.; LERARIO, Antonio Marcondes; MACHADO, Aline Zamboni; MORAES, Daniela Rodrigues de; SILVA, Thatiana Evilen da; ARNHOLD, Ivo J. P.; BATISTA, Rafael Loch; FARIA JUNIOR, Jose Antonio Diniz; COSTA, Elaine F.; NISHI, Mirian Y.; INACIO, Marlene; DOMENICE, Sorahia; MENDONCA, Berenice B.BackgroundFollow-up data on patients with 46,XY partial gonadal dysgenesis (PGD) until adulthood are scarce, making information on prognosis difficult. ObjectiveTo analyse the long-term outcomes of patients with 46,XY PGD regarding testosterone production, germ cell tumour risk, genotype and psychosexual adaptation. MethodsA retrospective longitudinal study of 33 patients (20 assigned male and 13 patients assigned female at birth). Molecular diagnosis was performed by Sanger sequencing or by targeted massively parallel sequencing of 63 genes related to disorders of sex development (DSDs). ResultsAge at first and last visit ranged from 0.1 to 43 and from 17 to 53years, respectively. Spontaneous puberty was observed in 57% of the patients. During follow-up, six of them had a gonadectomy (four due to female gender, and two because of a gonadal tumour). At last evaluation, five of six patients had adult male testosterone levels (median 16.7nmol/L, range 15.3-21.7nmol/L) and elevated LH and FSH levels. Germ cell tumours were found in two postpubertal patients (one with an abdominal gonad and one patient with Frasier syndrome). Molecular diagnosis was possible in 11 patients (33%). NR5A1 variants were the most prevalent molecular defects (n=6), and four of five patients harbouring them developed spontaneous puberty. Gender change was observed in four patients, two from each sex assignment group; all patients reported satisfaction with their gender at final evaluation. Sexual intercourse was reported by 81% of both gender and 82% of them reported satisfaction with their sexual lives. ConclusionSpontaneous puberty was observed in 57% of the patients with 46,XY PGD, being NR5A1 defects the most prevalent ones among all the patients and in those with spontaneous puberty. Gender change due to gender dysphoria was reported by 12% of the patients. All the patients reported satisfaction with their final gender, and most of them with their sexual life.
- Androgen receptor mRNA analysis from whole blood: a low-cost strategy for detection of androgen receptor gene splicing defects(2018) SILVA, Juliana M.; BATISTA, Rafael Loch; RODRIGUES, Andresa De Santi; NISHI, Mirian Y.; COSTA, Elaine M. F.; DOMENICE, Sorahia; CARVALHO, Luciani R. S.; MENDONCA, Berenice B.
- 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.