RAFAEL LOCH BATISTA
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with Partial Androgen Insensitivity Syndrome in an Individual with 47, XXY Karyotype(2017) BATISTA, Rafael L.; RODRIGUES, Andresa S.; NISHI, Mirian Y.; FEITOSA, Alina C. R.; GOMES, Nathalia L. R. A.; JUNIOR, Jose Antonio F.; DOMENICE, Sorahia; COSTA, Elaine M. F.; MENDONCA, Berenice B. deThere are only 2 patients with 47, XXY karyotype and androgen receptor (AR) gene mutation reported in the literature, and both are diagnosed as complete androgen insensitivity syndrome (CAIS). We report a 22-year-old female with 47, XXY karyotype and atypical external genitalia. Sequencing of AR revealed the heterozygous p.Asn849Lys*32 mutation, and extensive X chromosome microsatellite analysis showed homozygosity for Xp and heterozygosity for Xq, suggesting partial X maternal isodisomy. Partial androgen insensitivity syndrome (PAIS) developed in this case, probably because of the presence of the heterozygous AR mutation and random X-inactivation of the healthy allele. This is the first report of a female patient with 47, XXY karyotype and PAIS phenotype. (C) 2017 S.Karger AG, Basel
conferenceObject 46,XY Partial gonadal dysgenesis; diagnosis and long-term outcome at puberty(2022) CUCCARO, Rieko Tadokoro; HUGHES, Ieuan; COOLS, Martine; VIJVER, Koen van de; MENDONCA, Berenice Bilharinho de; DOMENICE, Sorahia; BATISTA, Rafael L.; DALLAGO, Renata Thomazini; GOMES, Nathalia Lisboa; COSTA, Elaine F.; MACIEL-GUERRA, Andrea T.; GUERRA-JUNIOR, Gil; ANDRADE, Juliana Gabriel Ribeiro de; LUCAS-HERALD, Angela; BRYCE, Jillian; HANNEMA, Sabine; JUUL, Anders; GLOBA, Eugenia; ELREAVEY, Kenneth M.; BARONIO, Federico; DACAL, Jimena Lopez; DARENDELILER, Feyza; POYRAZOGLU, Sukran; KOLESINSKA, Zofia; NIEDZIELA, Marek; CLAAHSEN, Hedi; AKKER, Erica L. T. van den; HERRMANN, Gloria; ATAPATTU, Navoda; JAIN, Vandana; SHARMA, Rajni; BETTERDORF, Markus; KONRAD, Daniel; HOLTERHUS, Paul Martin; FICA, Simona; SKAE, Mars; RUSSO, Gianni; STANCAMPIANO, Marianna Rita; GAZDAGH, Gabriella; DAVIES, Justin H.; MOHAMED, Zainaba; SENEVIRATNE, Sumudu Nimali; GURAN, Tulay; GUVEN, Ayla; WASNIEWSKA, Malgorzata; MLADENOV, Vilhelm; VERKAUSKAS, Gilvydas; MARKOSYAN, Renata; KORBONITS, Marta; HIORT, Olaf; WAGNER, IsabelViola; AHMED, S. Faisal; THANKAMONY, Ajay- Variants in 46,XY DSD-Related Genes in Syndromic and Non-Syndromic Small for Gestational Age Children with Hypospadias(2022) BRAGA, B. L.; GOMES, N. L.; NISHI, M. Y.; FREIRE, B. L.; BATISTA, R. L.; FARIA JUNIOR, J. A. D.; FUNARI, M. F. A.; BENEDETTI, A. F. F.; NARCIZO, A. De Moraes; CARDOSO, L. Cavalca; LERARIO, A. M.; GUERRA-JUNIOR, G.; COSTA, E. M. F.; DOMENICE, S.; JORGE, A. A. L.; MENDONCA, B. B.Hypospadias is a common congenital disorder of male genital formation. Children born small for gestational age (SGA) present a high frequency of hypospadias of undetermined etiology. No previous study investigated the molecular etiology of hypospadias in boys born SGA using massively parallel sequencing. Our objective is to report the genetic findings of a cohort of patients born SGA with medium or proximal hypospadias. We identified 46 individuals with this phenotype from a large cohort of 46,XY DSD patients, including 5 individuals with syndromic features. DNA samples from subjects were studied by either whole exome sequencing or target gene panel approach. Three of the syndromic patients have 5 main clinical features of Silver-Russell syndrome (SRS) and were first studied by MLPA. Among the syndromic patients, loss of DNA methylation at the imprinting control region H19/IGF2 was identified in 2 individuals with SRS clinical diagnosis. Two novel pathogenic variants in compound heterozygous state were identified in the CUL7 gene establishing the diagnosis of 3M syndrome in one patient, and a novel homozygous variant in TRIM37 was identified in another boy with Mulibrey nanism phenotype. Among the non-syndromic subjects, 7 rare heterozygous variants were identified in 6 DSD-related genes. However, none of the variants found can explain the phenotype by themselves. In conclusion, a genetic defect that clarifies the etiology of hypospadias was not found in most of the non-syndromic SGA children, supporting the hypothesis that multifactorial causes, new genes, and/or unidentified epigenetic defects may have an influence in this condition.
- The Molecular Basis of 5 alpha-Reductase Type 2 Deficiency(2022) BATISTA, Rafael L.; MENDONCA, Berenice B.The 5 alpha-reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, playing a crucial role in male development. This enzyme is encoded by the SRD5A2 gene, which maps to chromosome 2 (2p23), consists of 5 exons and 4 introns, and encodes a 254 amino acid protein. Disruptions in this gene are the molecular etiology of a subgroup of differences of sex development (DSD) in 46,XY patients. Affected individuals present a large range of external genitalia undervirilization, ranging from almost typically female external genitalia to predominantly typically male external genitalia with minimal undervirilization, including isolated micropenis. This is an updated review of the implication of the SRD5A2 gene in 5 alpha-reductase type 2 enzyme deficiency. For that, we identified 451 cases from 48 countries of this particular 46,XY DSD from the literature with reported variants in the SRD5A2 gene. Herein, we present the SRD5A2 mutational profile, the SRD5A2 polymorphisms, and the functional studies related to SRD5A2 variants to detail the molecular etiology of this condition. (c) 2022 S. Karger AG, Base
- 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.
- WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease(2022) FERRARI, M. T. M.; WATANABE, A.; SILVA, T. E. Da; GOMES, N. L.; BATISTA, R. L.; NISHI, M. Y.; PAULA, L. C. P. De; COSTA, E. C.; COSTA, E. M. F.; CUKIER, P.; ONUCHIC, L. F.; MENDONCA, B. B.; DOMENICE, S.Wilms' tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of WT1 have been classically associated with Denys-Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between WT1 disorders has been frequently observed. New WT1 variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic WT1 variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of WT1 between exons 9 and 10. Two pathogenic missense WT1 variants were identified in two 46,XY individuals with Wilms' tumors; both patients were <1 year of age at the time of diagnosis. A novel WT1 variant, c.1453_1456 (p.Arg485Glyfs∗14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with WT1 variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.