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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Integrative and Analytical Review of the 5-Alpha-Reductase Type 2 Deficiency Worldwide(2020) BATISTA, Rafael Loch; MENDONCA, Berenice BilharinhoIntroduction: The conversion of testosterone into dihydrotestosterone is catalyzed by the 5 alpha-reductase type 2 enzyme which plays a crucial role in the external genitalia virilization. It is encoded by the SRD5A2 gene. Allelic variants in this gene cause a 46,XY DSD with no genotype-phenotype relationship. It was firstly reported in the early 70s from isolated clusters. Since then, several cases have been reported. Putting together, it will expand the knowledge on the molecular bases of androgen milieu. Methods: We searched for SRD5A2 allelic variants (AV) in the literature (PubMed, Embase, MEDLINE) and websites (ensembl, HGMD, ClinVar). Only cases with AV in both alleles, either in homozygous or compound heterozygous were included. The included cases were analyzed according to ethnicity, exon, domain, aminoacid (aa) conservation, age at diagnosis, sex assignment, gender reassignment, external genitalia virilization and functional studies. External genitalia virilization was scored using Sinnecker scale. Conservation analysis was carried out using the CONSURF platform. For categorical variables, we used X2 test and Cramer's V. Continuous variables were analyzed by t test or ANOVA. Concordance was estimated by Kappa. Results: We identified 434 cases of 5ARD2 deficiencies from 44 countries. Most came from Turkey (23%), China (17%), Italy (9%), and Brazil (7%). Sixty-nine percent were assigned as female. There were 70% of homozygous allelic variants and 30% compound heterozygous. Most were missense variants (76%). However, small indels (11%), splicing (5%) and large deletions (4%) were all reported. They were distributed along with all exons with exon 1 (33%) and exon 4 (25%) predominance. Allelic variants in the exon 4 (NADPH-binding domain) resulted in lower virilization (p<0.0001). The codons 55, 65, 196, 235 and 246 are hotspots making up 25% of all allelic variants. Most of them (76%) were located at conserved aa. However, allelic variants at non-conserved aa were more frequently indels (28% vs 6%; p<0.01). The overall rate of gender change from female to male ranged from 16% to 70%. The lowest rate of gender change from female to male occurred in Turkey and the highest in Brazil. External genitalia virilization was similar between those who changed and those who kept their assigned gender. The gender change rate was significantly different across the countries (V=0.44; p<0.001) even with similar virilization scores. Conclusion: 5ARD2 deficiency has a worldwide distribution. Allelic variants at the NADPH-ligand region cause lower virilization. Genitalia virilization influenced sex assignment but not gender change which was influenced by cultural aspects across the countries. Molecular diagnosis influenced on sex assignment, favoring male sex assignment in newborns with 5 alpha-reductase type 2 deficiency.
- Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development(2023) JR, Jose Antonio Diniz Faria; MORAES, Daniela R.; KULIKOWSKI, Leslie Domenici; BATISTA, Rafael Loch; GOMES, Nathalia Lisboa; NISHI, Mirian Yumie; ZANARDO, Evelin; NONAKA, Carolina Kymie Vasques; SOUZA, Bruno Solano de Freitas; MENDONCA, Berenice Bilharinho; DOMENICE, SorahiaBackground: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. Methods: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. Results: In two patients, the diagnosis of 46,XX SRY + DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. Conclusions: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD.
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 BilharinhoconferenceObject Clinical, psychological, and molecular aspects of a large androgen insensitivity syndrome cohort(2023) BATISTA, Rafael Loch; INACIO, Marlene; AFONSO, Ane Caroline; CARVALHO, Filomena; RAMOS, Raquel; CRAVEIRO, Flora; DALLAGO, Renata; FERRARI, Maria Tereza; BATATINHA, Julio; NISHI, Miriam; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoconferenceObject Final adult height in SRY-negative 46, XX ovotesticular differences of sex development individuals(2019) FERRARI, Maria Tereza Martins; RODRIGUES, Daniela Moraes; GOMES, Nathalia Lisboa; NISHI, Mirian Yumi; BATISTA, Rafael Loch; COSTA, Elaine Maria Frade; MENDONCA, Berenice Bilharinho; DOMENICE, Sorahia; CRUZ, Patricia Sales Marques; SIRCILI, Maria Helena- A recurrent synonymous mutation in the human androgen receptor gene causing complete androgen insensitivity syndrome(2017) BATISTA, Rafael Loch; RODRIGUES, Andresa di Santi; NISHI, Mirian Yumie; GOMES, Nathalia Lisboa; FARIA JUNIOR, Jose Antonio Diniz; MORAES, Daniela Rodrigues de; CARVALHO, Luciani Renata; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoAndrogen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders of sex development (46,XY DSD). This syndrome is an X-linked inheritance disease and it is caused by mutations in the human androgen receptor (AR) gene. Non-synonymous point AR mutations are frequently described in this disease, including in the complete phenotype. We present a novel synonymous mutation in the human AR gene (c.1530C > T) in four 46,XY patients from two unrelated families associated with complete androgen insensitivity syndrome (CAIS). The analysis of mRNA from testis showed that synonymous AR mutation changed the natural exon 1 donor splice site, with deletion of the last 92 nucleotides of the AR exon 1 leading to a premature stop codon 12 positions ahead resulting in a truncate AR protein. Linkage analyses suggested a probable founder effect for this mutation. In conclusion, we described the first synonymous AR mutation associated with CATS phenotype, reinforcing the disease-causing role of synonymous mutations
- Elevated plasma miR-210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development(2022) ELIAS, Felipe Martins; NISHI, Mirian Yumi; SIRCILI, Maria Helena Palma; BASTISTA, Rafael Loch; GOMES, Nathalia Lisboa; FERRARI, Maria Tereza Martins; COSTA, Elaine Maria Frade; DENES, Francisco Tibor; MENDONCA, Berenice Bilharinho; DOMENICE, SorahiaBackground: Differences of sex development (DSD) is a term used for conditions in which the chromosomal, gonadal or phenotypical sex is atypical. 46,XY DSD patients frequently present undervirilized external genitalia. The expression of different miRNAs in many organs of the male genital system has been reported, and these miRNAs have been associated with testicular function and its disorders, but no description has been related to DSD conditions. This study aimed to evaluate the plasma expression of miR-210 in 46,XY DSD patients who presented atypical genitalia at birth. Methods: Eighteen 46,XY DSD patients who presented atypical genitalia (undescended testis and/or hypospadias, bifid scrotum or micropenis) at birth and 36 male control individuals were selected. Plasma levels of miR-210 and reference miR-23a were measured using RT-qPCR and the data were analysed by the 2(-Delta Ct) method. Results: MiR-210 plasma levels were significantly higher in 46,XY DSD patients with atypical genitalia than in male control subjects (p = 0.0024). A positive association between miR-210 levels and the presence of cryptorchidism and hypospadias (p = 0.0146 and p = 0.0223) was found in these patients. Significantly higher levels of miR-210 were observed in patients with 46,XY DSD and cryptorchidism than in control subjects (p = 0.0118). These results are in agreement with previous literature reports, in which increased levels of miR-210 expression were observed in human testicular tissue from adult males with undescended testes in comparison with samples of descended testes. Conclusion: Our study showed a positive association between the presence of atypical genitalia and plasma levels of miR-210 expression in the group of patients with 46,XY DSD of unknown aetiology studied. These findings contribute to reveal a new perspective on the role of miRNAs in the development of male external genitalia and the broad spectrum of phenotypes presented by patients with 46,XY DSD.
- Testosterone replacement in androgen insensitivity: is there an advantage?(2018) BATISTA, Rafael Loch; MENDONCA, Berenice Bilharinho
- Sexuality and fertility desire in a large cohort of individuals with 46, XY differences in sex development(2023) BATISTA, Rafael Loch; INACIO, Marlene; BRITO, Vinicius Nahime; SIRCILI, Maria Helena Palma; BAG, Min Jeong; GOMES, Nathalia Lisboa; COSTA, Elaine Maria Frade; DOMENICE, Sorahia; MENDONCA, Berenice BilharinhoObjective: To analyze aspects of sexual life and fertility desire among 46, XY DSD people, including those who changed their gender. Methods: It is a cross-sectional study including 127 adults (> 16 years of age) with 46, XY DSD (83 females; 44 males) from a Single Brazilian Tertiary-Care Medical Center. Results: Sexual fantasies and masturbation were more frequent in 46, XY DSD males, whereas orgasm and sexual life satisfaction were similar in both genders. More 46, XY DSD men than women had a long-term romantic relationship. 46, XY DSD women with prenatal androgen exposure reported more fear of being romantically rejected. External genitalia appearance at birth did not impact the sexuality of 46, XY DSD women after surgical genital treatment had been completed. Overall, the sexual life was similar between 46, XY men assigned as males and those who changed to the male gender. Regarding sexual orientation, most self-reported as heterosexual (91% and 92% of women and men, respectively). The desire for fertility had a similar prevalence in both genders, but more women than men considered infertility a barrier to a long-term romantic relationship. Twelve individuals (7 males) had children; 10 out of 12 have adopted children. Conclusion: Fertility desire was shared among 46, XY DSD people, regardless of gender. Prenatal androgen exposure reduced the desire for motherhood in 46, XY women. 46, XY DSD people who changed from female to male gender presented similar sexual parameters as those assigned as males. Among females, virilized genitalia at birth did not affect sexuality once the surgical treatment is completed.
- Vasculometabolic effects in patients with congenital growth hormone deficiency with and without GH replacement therapy during adulthood(2021) BISCOTTO, Isabela Peixoto; HONG, Valeria Aparecida Costa; BATISTA, Rafael Loch; MENDONCA, Berenice Bilharinho; ARNHOLD, Ivo Jorge Prado; BORTOLOTTO, Luiz Aparecido; CARVALHO, Luciani Renata SilveiraPurpose To evaluated the metabolic profiles and vascular properties in congenital growth hormone (GH) deficiency (GHD) and its replacement in adults. Patients and methods Cross-sectional study conducted in a single tertiary center for pituitary diseases. Eighty-one adult subjects were divided into three groups: (1) 29 GHD patients with daily subcutaneous GH replacement therapy (GHRT) during adulthood; (2) 20 GHD patients without GHRT during adulthood and (3) 32 controls. Only patients with adequate adherence to others pituitary hormone deficiencies were included. Anthropometric parameters, body composition by dual-energy X-ray absorptiometry, metabolic profiles and vascular properties (carotid intima media thickness, pulse wave velocity and flow-mediated dilation) were compared among the groups. Results Waist-to-height ratio (WHR), body fat percentages and fat mass index (FMI) were lower in patients with GHRT than patients without GHRT during adulthood (0.49 +/- 0.06 vs. 0.53 +/- 0.06 p = 0.026, 30 +/- 10 vs. 40 +/- 11 p = 0.003 and 7.3 +/- 4 vs. 10 +/- 3.5 p = 0.041, respectively). In addition, association between longer GHRT and lower body fat percentage was observed (r = - 0.326, p = 0.04). We found higher triglyceride (113.5 +/- 62 vs. 78 +/- 36, p = 0.025) and lower HDL cholesterol (51 +/- 17 vs. 66 +/- 23, p = 0.029) levels in patients without GHRT during adulthood in comparison to controls. No statistical differences were observed for vascular properties among the groups. Conclusions No differences in vascular properties were observed in congenital GHD adult patients with or without GHRT despite patients without GHRT had an unfavorable body composition. GHRT currently remains an individualized decision in adults with GHD and these findings bring new insight into the treatment and follow-up of these patients.