MIRIAN YUMIE NISHI
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
conferenceObject Whole-Exome Sequencing Reveals RAD51B Variant in Two Sisters with Primary Ovarian Failure(2016) FRANCA, Monica; FUNARI, Mariana; NISHI, Mirian; DOMENICE, Sorahia; LATRONICO, Ana Claudia; JORGE, Alexander; LERARIO, Antonio; MENDONCA, Berenice- 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.
conferenceObject RAB3IP and DGCR8 as a Potentially Pathogenic Novel Candidate Gene Involving in Growth Disorders(2016) HOMMA, Thais; FUNARI, Mariana; LERARIO, Antonio; FREIRE, Bruna; NISHI, Mirian; YAMAMOTO, Guilherme; NASLAVSKY, Michel; ZATZ, Mayana; ARNHOLD, Ivo; JORGE, AlexanderconferenceObject Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Accordingly Gender Assignment(2016) GOMES, Nathalia; COSTA, Elaine; ZAMBONI, Aline; NISHI, Mirian; BATISTA, Rafael; CUNHA, Flavia; INACIO, Marlene; DOMENICE, Sorahia; MENDONCA, BereniceconferenceObject Final Adult Height of Patients with Disorders of Sex Development (DSD) Associated with Sex Chromosome Abnormalities 45,X/46,XY or 45,X/46,X,+Y Variants(2016) FARIA JUNIOR, J. A. D.; GOMES, N. L.; BATISTA, R. L.; MORAES, D. R.; SCALCO, R.; NISHI, M. Y.; JORGE, A. A. L.; ULTRA, M. A. M. S.; COSTA, E. M. F.; MENDONCA, B. B.; DOMENICE, S.- Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line(2016) RIBEIRO, T. C.; JORGE, A. A.; MONTENEGRO, L. R.; ALMEIDA, M. Q.; FERRAZ-DE-SOUZA, B.; NISHI, M. Y.; MENDONCA, B. B.; LATRONICO, A. C.Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (#1 and #2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF1R siRNA #1 or #2. Relative expression of IGF1R mRNA decreased approximately 50 % and Western blot analysis revealed a 30 % of reduction in IGF-1R protein. Downregulation of this gene resulted in 40 % reduction in cell growth in vitro and 45 % increase in apoptosis using siRNA #2. These findings demonstrate that decreasing IGF1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF-1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.
- Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure(2016) SOUSA, Braian Lucas A.; NISHI, Mirian Yumie; SANTOS, Mariza Gerdulo; BRITO, Vinicius Nahime; DOMENICE, Sorahia; MENDONCA, Berenice B.OBJECTIVES: Primary ovarian failure is a rare disorder, and approximately 90% of cases are of unknown etiology. The aim of this study was to search for mutations in NANOS3, a gene that was recently related to the etiology of primary ovarian failure, in a group of Brazilian women. METHODS: We screened for NANOS3 DNA variants in 30 consecutive women who were previously diagnosed with primary ovarian failure, of unknown etiology and compared the results with those from 185 women with normal fertility. The NANOS3 gene was amplified by polymerase chain reaction using pairs of specific primers and then sequenced. The resulting sequences were compared with control sequences available in the National Center for Biotechnology and Information database. RESULTS: No mutations in NANOS3 were found in primary ovarian failure patients, but four previously described polymorphisms were identified at a similar frequency in the control and primary ovarian failure groups. CONCLUSIONS: Mutations in NANOS3 were not associated with primary ovarian failure in the present cohort.
- Good response to long-term therapy with growth hormone in a patient with 9p trisomy syndrome: A case report and review of the literature(2016) CANTON, Ana Pinheiro Machado; NISHI, Mirian Yumie; FURUYA, Tatiane Katsue; ROELA, Rosimeire Aparecida; JORGE, Alexander Augusto LimaThe 9p trisomy syndrome is a rare condition, clinically characterized by a wide range of dysmorphic features, intellectual disability, and, in most patients, by short stature. Recombinant human growth hormone (rhGH) therapy is still controversial in syndromic disorders, the reason for which it is not currently indicated. Here we report a 7-year-old boy with 9p trisomy syndrome and marked short stature. Results of routine laboratory assessments were normal. IGF1 and IGFBP3 levels were both in the normal range (-1.6 and -0.7 SDS, respectively). GH peak in response to oral clonidine stimulation test was 3.5g/L, which is considered a normal response. Chromosomal analysis revealed the karyotype 47,XY,+del(9)(pter-q11:) dn. SNP array data indicated absence of mosaicism [arr 9p24.3-p13.1 (203,861-38,787,480) x3]. By the age of 8.3 years, the patient had persistent short stature (-2.9 SDS) with normal growth velocity (4.9cm/y; -0.7 SDS), not showing spontaneous catch-up. After 5.6 years of rhGH therapy (50g/kg/d), height SDS improved from -2.9 to -1.0. This result suggests that rhGH therapy could be considered for patients with 9p trisomy syndrome who present with short stature. The degree of intellectual disability and the potential for social inclusion should be taken into account when recommending this treatment. Additional studies are needed to establish the benefits of height gain in these patients. (c) 2015 Wiley Periodicals, Inc.
conferenceObject A New GNRH1 Mutation in a Boy with Congenital Isolated Hypogonadotropic Hypogonadism(2016) LIMA, L. Guimaraes; MONTENEGRO, L. Ribeiro; LERARIO, A. Marcondes; NISHI, M.; MENDONCA, B. B.; LATRONICO, A. C.; SILVEIRA, L. Ferreira GontijoconferenceObject Targeted Massively Parallel Sequencing for the Molecular Diagnosis of 46, XY Disorders of Sex Development (DSD)(2016) GOMES, N. L.; LERARIO, A. M.; FRANCA, M. M.; NISHI, M. Y.; FUNARI, M. F.; COSTA, E. M. F.; FARIA JUNIOR, J. A. D.; BATISTA, R. L.; DOMENICE, S.; MENDONCA, B. B.