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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Genetic Predictors of Long-Term Response to Growth Hormone (GH) Therapy in Children With GH Deficiency and Turner Syndrome: The Influence of a SOCS2 Polymorphism(2014) BRAZ, Adriana F.; COSTALONGA, Everlayny F.; TRARBACH, Ericka B.; SCALCO, Renata C.; MALAQUIAS, Alexsandra C.; GUERRA-JUNIOR, Gil; ANTONINI, Sonir R. R.; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; JORGE, Alexander A. L.Background: There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling. Objective: The objective of the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms on adult height of patients treated with recombinant human GH (rhGH). Design and Patients: Genotypes were correlated with adult height data of 65 Turner syndrome (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear regressions. Generalized multifactor dimensionality reduction was used to evaluate gene-gene interactions. Results: Baseline clinical data were indistinguishable among patients with different genotypes. Adult height SD scores of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P < .003), GHR-exon 3 (P = .016) and -202 A/C IGFBP3 (P = .013) polymorphisms, together with clinical factors accounted for 58% of the variability in adult height and 82% of the total height SD score gain. Patients harboring any two negative genotypes in these three different loci (homozygosity for SOCS2 T allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were more likely to achieve an adult height at the lower quartile (odds ratio of 13.3; 95% confidence interval of 3.2-54.2, P = .0001). Conclusion: The SOCS2 polymorphism (rs3782415) has an influence on the adult height of children with TS and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and SOCS2 loci have an influence on the growth outcomes of TS and GHD patients treated with rhGH. The use of these genetic markers could identify among rhGH-treated patients those who are genetically predisposed to have less favorable outcomes.
- 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.
- IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children(2019) INOUE-LIMA, Thais H.; VASQUES, Gabriela A.; SCALCO, Renata C.; NAKAGUMA, Marilena; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; JORGE, Alexander A. L.Background: When evaluating peripubertal short stature patients, the interpretation of insulin-like growth factor 1 (IGF-1) levels based on chronological age (CA) can be inaccurate due to the influence of sex steroids and, presently, there is no evidence to support the assessment of IGF-1 values according to bone age (BA) and pubertal status (PS). Our objective was to assess the discriminatory performance of IGF-1 levels based on CA, BA and PS in the diagnosis of growth hormone (GH) deficiency. Methods: We evaluated IGF-1 levels from 154 peripubertal short stature patients classified as GH deficient (GHD, n = 23) or non-GHD (n =131). IGF-1 was assayed by a chemiluminescent immunometric assay and transformed into standard deviation scores (SDS) according to CA (IGF1-SDS-CA), BA (IGF-1-SDS-BA) and PS (IGF-1-SDS-PS). Results: The performances of IGF-1-SDS-CA, IGF-1-SDS-BA and IGF-1-SDS-PS in the receiver operator characteristics (ROC) curves were similar. There were greater accuracy and specificity of IGF-1-SDS-PS (98A% and 93.3%, respectively) and IGF-1-SDS-BA (92.7% and 90.1%, respectively) when compared to IGF-1-SDS-CA (65.6% and 69.5%, respectively). The post-test probability of the IGF-1-SDS was also improved when compared to PS and BA - 44.8% (IGF-1-SDS-PS), 16.8% (IGF-1-SDS-BA) and 5.1% (IGF-1-SDS-CA), with similar negative predictive values. Conclusions: The evaluation of IGF-1 levels based on CA has a higher sensitivity than those based on BA or PS, which justify its use as a screening tool. Additionally, IGF-1 assessed by PS has the best positive predictive power for GHD diagnosis in peripubertal age and could reduce the necessity of a second Gil stimulation test.
- The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for SHOX Analysis(2013) MALAQUIAS, Alexsandra C.; SCALCO, Renata C.; FONTENELE, Eveline G. P.; COSTALONGA, Everlayny F.; BALDIN, Alexandre D.; BRAZ, Adriana F.; FUNARI, Mariana F. A.; NISHI, Mirian Y.; GUERRA-JUNIOR, Gil; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; JORGE, Alexander A. L.Aims: To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for SHOX analysis. Methods: Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with SHOX defects (SHOX-D) and 193 females with Turner syndrome (TS). Results: The frequency of abnormal body proportion, defined as SH/H SDS > 2, in ISS children was 16.4% (95% CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p < 0.001). The SHOX gene was evaluated in all disproportionate ISS children and defects in this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95% CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS > 2 were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20-36%) with TS. Conclusion: Abnormal body proportions were observed in almost all individuals with SHOX-D, 50% of females with TS and 16% of children considered ISS. Defects in SHOX gene were identified in 19% of ISS children with SH/H SDS > 2, suggesting that SH/H SDS is a useful tool to select children for undergoing SHOX molecular studies. (C) 2013 S. Karger AG, Basel
- 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.
- Adult Height in 299 Patients with Turner Syndrome with or without Growth Hormone Therapy: Results and Literature Review(2021) DANTAS, Naiara C. B.; BRAZ, Adriana F.; MALAQUIAS, Alexsandra; LEMOS-MARINI, Sofia; ARNHOLD, Ivo J. P.; SILVEIRA, Ester R.; ANTONINI, Sonir R.; GUERRA-JUNIOR, Gil; MENDONCA, Berenice; JORGE, Alexander; SCALCO, Renata C.Context: Treatment with growth hormone (GH) is considered effective in improving adult height (AH) in Turner syndrome (TS). However, there are few studies comparing AH between treated patients and a concurrent untreated group. Objective: To assess the efficacy of GH treatment in improving AH in TS and to review previous published studies with treated and untreated groups. Participants and Methods: We retrospectively analyzed clinical data and AH of a large cohort of GH-treated (n = 168) and untreated (n = 131) patients with TS. Data are shown as median and interquartile range (IQR). We assessed pretreatment variables related with AH and compared our results with 16 studies that also included an untreated group. Results: The GH-treated group was 6.2 cm taller than the untreated group (AH = 149 cm [IQR 144.5-152.5 cm] vs. 142.8 cm [IQR 139-148 cm], p < 0.001) after 4.9 years of GH treatment with a dose of 0.35 mg/kg/week. AH SDS corrected for target height (TH) was 7.2 cm higher in GH-treated patients. AH SDS >=-2 was more frequent in GH-treated patients (43%) than in untreated patients (16%, p < 0.001). AH SDS was also more frequently within the TH range in the GH-treated group (52%) than in the untreated group (15%, p < 0.001). Height SDS at start of GH therapy and TH SDS were positively correlated with AH (p < 0.001; R-2 = 0.375). Considering the current result together with previous similar publications, a mean AH gain of 5.7 cm was observed in GH-treated (n = 696) versus untreated (n = 633) patients. Conclusions: Our study strengthens the evidence for efficacy of GH therapy in patients with TS from different populations.