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
16 resultados
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- STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability(2015) SCALCO, Renata C.; HWA, Vivian; DOMENE, Horacio M.; JASPER, Hector G.; BELGOROSKY, Alicia; MARINO, Roxana; PEREIRA, Alberto M.; TONELLI, Carlos A.; WIT, Jan M.; ROSENFELD, Ron G.; JORGE, Alexander A. L.Context and objective: GH insensitivity with immune dysfunction caused by STAT5B mutations is an autosomal recessive condition. Heterozygous mutations in other genes involved in growth regulation were previously associated with a mild height reduction. Our objective was to assess for the first time the phenotype of heterozygous STAT5B mutations. Methods: We genotyped and performed clinical and laboratory evaluations in 52 relatives of two previously described Brazilian brothers with homozygous STAT5B c.424_427del mutation (21 heterozygous). Additionally, we obtained height data and genotype from 1104 adult control individuals from the same region in Brazil and identified five additional families harboring the same mutation (18 individuals, 11 heterozygous). Furthermore, we gathered the available height data from first-degree relatives of patients with homozygous STAT5B mutations (17 individuals from seven families). Data from heterozygous individuals and non-carriers were compared. Results: Individuals carrying heterozygous STAT5B c.424_427del mutation were 0.6 SDS shorter than their non-carrier relatives (P=0.009). Heterozygous subjects also had significantly lower SDS for serum concentrations of IGF1 (P=0.028) and IGFBP3 (P=0.02) than their non-carrier relatives. The 17 heterozygous first-degree relatives of patients carrying homozygous STAT5B mutations had an average height SDS of -1.4 +/- 0.8 when compared with population-matched controls (P<0.001). Conclusions: STAT5B mutations in the heterozygous state have a significant negative impact on height (similar to 3.9 cm). This effect is milder than the effect seen in the homozygous state, with height usually within the normal range. Our results support the hypothesis that heterozygosity of rare pathogenic variants contributes to normal height heritability.
- 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.
- Deficiência da STAT5B : uma nova síndrome de insensibilidade ao hormônio de crescimento associada a acometimento imunológico(2013) SCALCO, Renata C.; PUGLIESE-PIRES, Patricia N.; JORGE, Alexander A. L.A new presentation of growth hormone insensitivity (GHI) caused by homozygous mutations in STAT5B (signal transducer and activator of transcription 5B) gene has been characterized in the last years. Its particularity is the association with severe immune dysfunction, especially with lymphocytic interstitial pneumonitis. This may mislead physicians into considering short stature as secondary to chronic immunological disease and consequently into underdiagnosing this form of GHI. The objective of this review is to propagate current knowledge about this rare pathology, facilitating the diagnosis of patients with GHI due to STAT5B mutations in endocrinology and other specialties clinics. Arq Bras Endocrinol Metab. 2013;57(5):333-8
conferenceObject Evidence for a Founder Effect of C.424_427del STAT5B Mutation Causing Growth Hormone Insensitivity in the South of Brazil(2014) SCALCO, Renata Da Cunha; FUNARI, Mariana Ferreira de Assis; ARACAVA, Rosana Midori; TONELLI, Carlos Andre; JORGE, Alexander Augusto LimaconferenceObject 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.- 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.
- Diagnostic and therapeutic approach of tall stature(2017) ALBUQUERQUE, Edoarda V. A.; SCALCO, Renata C.; JORGE, Alexander A. L.Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitutional advance of growth (generally associated with obesity), both of which are diagnoses of exclusion. It is necessary to have familiarity with a large number of rarer overgrowth syndromes, especially because some of them may have severe complications such as aortic aneurysm, thromboembolism and tumor predisposition and demand-specific follow-up approaches. Additionally, endocrine disorders associated with tall stature have specific treatments and for this reason their recognition is mandatory. With this review, we intend to provide an up-to-date summary of the genetic conditions associated with overgrowth to emphasize a practical diagnostic approach of patients with tall stature and to discuss the limitations of current growth interruption treatment options.
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.- 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