RENATA DA CUNHA SCALCO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
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Resultados de Busca
Agora exibindo 1 - 8 de 8
- Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature(2022) ANDRADE, Nathalia Liberatoscioli Menezes; FUNARI, Mariana Ferreira de Assis; MALAQUIAS, Alexsandra Christianne; COLLETT-SOLBERG, Paulo Ferrez; GOMES, Nathalia L. R. A.; SCALCO, Renata; DANTAS, Naiara Castelo Branco; REZENDE, Raissa C.; TIBURCIO, Angelica M. F. P.; SOUZA, Micheline A. R.; FREIRE, Bruna L.; V, Ana C. Krepischi; LONGUI, Carlos Alberto; LERARIO, Antonio Marcondes; ARNHOLD, Ivo J. P.; JORGE, Alexander A. L.; VASQUES, Gabriela AndradeObjectiveMost children with short stature remain without an etiologic diagnosis after extensive clinical and laboratory evaluation and are classified as idiopathic short stature (ISS). This study aimed to determine the diagnostic yield of a multigene analysis in children classified as ISS. Design and methodsWe selected 102 children with ISS and performed the genetic analysis as part of the initial investigation. We developed customized targeted panel sequencing, including all genes already implicated in the isolated short-stature phenotype. Rare and deleterious single nucleotide or copy number variants were assessed by bioinformatic tools. ResultsWe identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%). Three patients had more than one P/LP genetic alteration. Most of the findings were in genes associated with the growth plate differentiation: IHH (n = 4), SHOX (n = 3), FGFR3 (n = 2), NPR2 (n = 2), ACAN (n = 2), and COL2A1 (n = 1) or involved in the RAS/MAPK pathway: NF1 (n = 2), PTPN11 (n = 1), CBL (n = 1), and BRAF (n = 1). None of these patients had clinical findings to guide a candidate gene approach. The diagnostic yield was higher among children with severe short stature (35% vs 12.2% for height SDS <= or > -3; P = 0.034). The genetic diagnosis had an impact on clinical management for four children. ConclusionA multigene sequencing approach can determine the genetic etiology of short stature in up to one in six children with ISS, removing the term idiopathic from their clinical classification.
conferenceObject Girls with short statute and Xp22;Yq11 translocation: should a prophylactic gonadectomy be recommended ?(2023) DANTAS, Naiara C. B.; FUNARI, Mariana F. A.; ANDRADE, Nathalia L. M.; REZENDE, Raissa C.; CELLIN, Laurana P.; CRISOSTOMO, Lindiane G.; SCALCO, Renata C.; JORGE, Alexander A. L.conferenceObject Retrospective Analysis of Individuals with Differences in Sex Development (DSD) in a Brazilian Single-Center Study Across the Lifespan(2023) BATISTA, Rafael; GOMES, Nathalia; BACHEGA, Tania; MADUREIRA, Guiomar; MIRANDA, Mirela; DALLAGO, Renata; TERESA, Maria; LOUSADA, Ferrari Lia; CRAVEIRO, Flora; BATATINHA, Julio; SCALCO, Renata; JORGE, Alexander; COSTA, Elaine; SIRCILI, Maria Helena; DENES, Francisco; INACIO, Marlene; NISHI, Mirian; DOMENICE, Sorahia; MENDONCA, Berenice- ESR1 polymorphism (rs2234693) influences femoral bone mass in patients with Turner syndrome(2019) SCALCO, Renata C.; TRARBACH, Ericka B.; ALBUQUERQUE, Edoarda V. A.; HOMMA, Thais K.; INOUE-LIMA, Thais H.; NISHI, Mirian Y.; MENDONCA, Berenice B.; JORGE, Alexander A. L.Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 t 0.065 g/cm(2)vs 0.822 +/- 0.113 g/cm(2), P = 0.008) and total hip BMD (0.777 +/- 0.118 g/cm(2)vs 0.903 +/- 0.098 g/cm(2), P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 +/- 0.049 vs 0.820 +/- 0.105 g/cm(2), P = 0.0047) and total hip BMD (0.752 +/- 0.093 vs 0.908 +/- 0.097 g/cm(2), P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.
conferenceObject A prospective genetic analysis of children with idiopathic short stature (ISS) using whole-exome sequencing (WES): first results(2023) CELLIN, Laurana P.; ANDRADE, Nathalia L. M.; REZENDE, Raissa C.; SOUZA, Vinicius de; DANTAS, Naiara C. B.; QUEDAS, Elisangela P. S.; FUNARI, Mariana F. A.; VASQUES, Gabriela A.; SCALCO, Renata C.; MALAQUIAS, Alexsandra A. C.; JORGE, Alexander A. L.- Identification of a second genetic alteration in patients with SHOX deficiency individuals: a potential explanation for phenotype variability(2023) DANTAS, Naiara C. B.; FUNARI, Mariana F. A.; LERARIO, Antonio M.; ANDRADE, Nathalia L. M.; REZENDE, Raissa C.; CELLIN, Laurana P.; ALVES, Cresio; CRISOSTOMO, Lindiane G.; ARNHOLD, Ivo J. P.; MENDONCA, Berenice; SCALCO, Renata C.; JORGE, Alexander A. L.Objective Our study aimed to assess the impact of genetic modifiers on the significant variation in phenotype that is observed in individuals with SHOX deficiency, which is the most prevalent monogenic cause of short stature.Design and methods We performed a genetic analysis in 98 individuals from 48 families with SHOX deficiency with a target panel designed to capture the entire SHOX genomic region and 114 other genes that modulate growth and/or SHOX action. We prioritized rare potentially deleterious variants.Results We did not identify potential deleterious variants in the promoter or intronic regions of the SHOX genomic locus. In contrast, we found eight heterozygous variants in 11 individuals from nine families in genes with a potential role as genetic modifiers. In addition to a previously described likely pathogenic (LP) variant in CYP26C1 observed in two families, we identified LP variants in PTHLH and ACAN, and variants of uncertain significance in NPR2, RUNX2, and TP53 in more affected individuals from families with SHOX deficiency. Families with a SHOX alteration restricted to the regulatory region had a higher prevalence of a second likely pathogenic variant (27%) than families with an alteration compromising the SHOX coding region (2.9%, P = .04).Conclusion In conclusion, variants in genes related to the growth plate have a potential role as genetic modifiers of the phenotype in individuals with SHOX deficiency. In individuals with SHOX alterations restricted to the regulatory region, a second alteration could be critical to determine the penetrance and expression of the phenotype.
- Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect(2017) SCALCO, Renata C.; GONCALVES, Fernanda T.; SANTOS, Hadassa C.; CARDENA, Mari M. S. G.; TONELLI, Carlos A.; FUNARI, Mariana F. A.; ARACAVA, Rosana M.; PEREIRA, Alexandre C.; FRIDMAN, Cintia; JORGE, Alexander A. L.Homozygous STAT5B mutations causing growth hormone insensitivity with immune dysfunction were described in 10 patients since 2003, including two Brazilian brothers from the south of Brazil. Our objectives were to evaluate the prevalence of their STAT5B mutation in this region and to analyze the presence of a founder effect. We obtained DNA samples from 1,205 local inhabitants, 48 relatives of the homozygous patients and four individuals of another affected family. Genotyping forSTAT5B c.424_427del mutation and for two polymorphic markers around it was done through fragment analysis technique. We also determined Y-chromosome and mtDNA haplotypes and genomic ancestry in heterozygous carriers. We identified seven families with STAT5B c.424_427del mutation, with 33 heterozygous individuals. The minor allelic frequency of this mutation was 0.29% in this population (confidence interval 95% 0.08-0.5%), which is significantly higher than the frequency of other pathogenic STAT5B allele variants observed in public databases (p < 0.001). All heterozygous carriers had the same haplotype present in the homozygous patients, found in only 9.4% of non-carriers (p < 0.001), supporting the existence of a founder effect. The Y-chromosome haplotype, mtDNA and genomic ancestry analysis indicated a European origin of this mutation. Our results provide compelling evidence for a founder effect of STAT5B c.424_427del mutation.
- Impact of Long-Term Dexamethasone Therapy on the Metabolic Profile of Patients With 21-Hydroxylase Deficiency(2019) SERAPHIM, Carlos E.; FRASSEI, Juliana S.; PESSOA, Bruna S.; SCALCO, Renata C.; MIRANDA, Mirela C.; MADUREIRA, Guiomar; MENDONCA, Berenice B.; BACHEGA, Tania A. S. S.Context: No consensus has been reached regarding the glucocorticoid (GC) to use for congenital adrenal hyperplasia (CAH) during adulthood. Dexamethasone (DEX), because of its longer half-life, could improve compliance; however, no data are available regarding the long-term effects of DEX therapy. Objective: To analyze the metabolic effect of DEX therapy for adults with CAH. Design: Retrospective analysis of a CAH cohort receiving DEX therapy. Setting: Medical School Hospital, Sao Paulo University, Brazil. Participants: Sixty patients with well-controlled classic CAH (41 women; 30 with salt-wasting) receiving DEX after achievement of final height. Interventions: None. Main Outcome Measures: Clinical, laboratory, and metabolic data were compared immediately before DEX and at the last evaluation. Results: The mean age at the last evaluation was 31.9 +/- 9.6 years, and the duration of DEX therapy was 11.5 +/- 4.9 years. The mean DEX dose was 0.18 +/- 0.07 mg/m(2)/d. The body mass index SD score (1.6 +/- 1.6 vs 1.5 +/- 1.5 mg/m(2); P = 0.65) and obesity prevalence (27% vs 27%) did not differ between evaluations. However, the waist/height ratio (WtHR) had increased from 0.54 +/- 0.08 to 0.56 +/- 0.1 (P = 0.001). An increase in the homeostatic model assessment for insulin resistance index (2.5 +/- 1.3 vs 2.8 +/- 1.7; P = 0.03) was observed and positively correlated with the WtHR (r = 0.54). The prevalence of metabolic syndrome (7% vs 10%; P = 0.7) and hypertension (15% vs 13.3%; P = 0.8) did not differ significantly between the two evaluations. Conclusions: Long-term and low-dose DEX therapy did not lead to increases in obesity or metabolic syndrome, although it was associated with an increased WtHR and greater homeostatic model assessment for insulin resistance observed with chronic use of GCs. DEX appears to be an acceptable option to treat adult CAH.