DEBORA ROMEO BERTOLA
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing(2019) HOMMA, Thais Kataoka; FREIRE, Bruna Lucheze; KAWAHIRA, Rachel Sayuri Honjo; DAUBER, Andrew; FUNARI, Mariana Ferreira de Assis; LERARIO, Antonio Marcondes; NISHI, Mirian Yumie; ALBUQUERQUE, Edoarda Vasco de; VASQUES, Gabriela de Andrade; COLLETT-SOLBERG, Paulo Ferrez; SUGAYAMA, Sofia Mizuho Miura; BERTOLA, Debora Romeo; KIM, Chong Ae; ARNHOLD, Ivo Jorge Prado; MALAQUIAS, Alexsandra Christianne; JORGE, Alexander Augusto de LimaObjective To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. Study design For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. Results Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. Conclusions The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.
- Noonan syndrome patients beyond the obvious phenotype: A potential unfavorable metabolic profile(2021) NORONHA, Renata M.; VILLARES, Sandra M. F.; TORRES, Natalia; QUEDAS, Elisangela P. S.; HOMMA, Thais Kataoka; ALBUQUERQUE, Edoarda V. A.; MORAES, Michelle B.; FUNARI, Mariana F. A.; BERTOLA, Debora R.; JORGE, Alexander A. L.; MALAQUIAS, Alexsandra C.Noonan syndrome (NS) and NS related disorders (NRD) are frequent monogenic diseases. Pathogenic variants in PTPN11 are observed in approximately 50% of these NS patients. Several pleiotropic phenotypes have previously been described in this condition. This study aimed at characterizing glucose and lipid profiles in patients with NS/NRD. We assessed fasting blood glucose, insulin, cholesterol (total and fractions), and triglyceride (TG) levels in 112 prepubertal children and 73 adults. Additionally, an oral glucose tolerance test (OGTT) was performed in 40 children and 54 adults. Data were analyzed between age groups according to the presence (+) or absence (-) of PTPN11 mutation. Prepubertal patients with NS/NRD were also compared with a control group. Despite the lean phenotype of children with NS/NRD, they presented an increased frequency of low HDL-cholesterol (63% in PTPN11+, 59% in PTPN11- and 16% in control, p < .001) and high TG levels (29% in PTPN11+, 18% in PTPN11- and 2.3% in control). PTPN11+ patients had a higher median HOMA-IR (1.0, ranged from 0.3 to 3.2) in comparison with PTPN11- (0.6; 0.2 to 4.4) and controls (0.6; 0.4 to 1.4, p = .027). Impaired glucose tolerance was observed in 19% (10:54) of lean adults with NS/NRD assessed by OGTT. Moreover, women with PTPN11 mutations had lower HDL-cholesterol levels than those without. Our results suggest that children and young adult patients with NS/NRD have an unfavorable metabolic profile characterized by low HDL, a tendency of elevated TGs, and glucose metabolism impairment despite a lean phenotype.
- Growth and Clinical Characteristics of Children with Floating-Harbor Syndrome: Analysis of Current Original Data and a Review of the Literature(2020) HOMMA, Thais K.; FREIRE, Bruna L.; HONJO, Rachel; DAUBER, Andrew; FUNARI, Mariana F. A.; LERARIO, Antonio M.; ALBUQUERQUE, Edoarda V. A.; VASQUES, Gabriela A.; BERTOLA, Debora R.; KIM, Chong A.; MALAQUIAS, Alexsandra C.; JORGE, Alexander A. L.Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by dysmorphic facial features, short stature, and expressive language delay. Objective: The aim of this study was to describe a cohort of patients with FHS and review the literature about the response to recombinant human growth hormone (rhGH) therapy. Methods: Anthropometric and laboratory data from 7 patients with FHS were described. The molecular diagnosis was established by multigene analysis. Moreover, we reviewed the literature concerning patients with FHS treated with rhGH. Results: All 7 patients were born small for gestational age. At first evaluation, 6 patients had a height standard deviation score (SDS) <=-2 and 1 had short stature in relation to their target height. Bone age was usually delayed, which rapidly advanced during puberty. Nonspecific skeletal abnormalities were frequently noticed, and normal to elevated plasma IGF-I levels were observed in all except 1 patient with growth hormone deficiency. Information about 20 patients with FHS treated with rhGH was analyzed (4 from our cohort and 16 from the literature). The median height changes during the treatment period (approx. 2.9 years) were 1.1 SDS (range from -0.4 to 3.1). Nontreated patients had an adult height SDS of -4.1 +/- 1.2 (n = 10) versus -2.6 +/- 0.8 SDS (n = 7, p 0.012) for treated patients. Conclusion: We observed a laboratory profile compatible with IGF-1 insensitivity in some patients with FHS. Nevertheless, our study suggests that children with FHS may be considered as candidates for rhGH therapy. Further studies are necessary to establish the real benefit and safety of rhGH therapy in these patients.
conferenceObject Children with Noonan and Noonan-Like Syndromes Had a Lipid Profile Resembling Metabolic Syndrome and Type 2 Diabetes(2015) MALAQUIAS, A.; HOMMA, T.; MORAES, M.; FUNARI, M.; PEREIRA, A.; VILLARES, S.; BERTOLA, D.; JORGE, A.- Impact of Growth Hormone Therapy on Adult Height in Patients with PTPN11 Mutations Related to Noonan Syndrome(2019) MALAQUIAS, Alexsandra C.; NORONHA, Renata M.; SOUZA, Thaiana T. O.; HOMMA, Thais K.; FUNARI, Mariana F. A.; YAMAMOTO, Guilherme L.; SILVA, Fernanda Viana; MORAES, Michelle B.; HONJO, Rachel S.; KIM, Chong A.; NESI-FRANCA, Suzana; CARVALHO, Julienne A. R.; QUEDAS, Elisangela P. S.; BERTOLA, Debora R.; JORGE, Alexander A. L.Objectives: The aim of this study was to evaluate the response to recombinant human growth hormone (rhGH) treatment in patients with Noonan syndrome (NS). Materials and Methods: Forty-two patients (35 PTPN11+) were treated with rhGH, and 17 were followed-up until adult height. The outcomes were changes in growth velocity (GV) and height standard deviation scores (SDS) for normal (height-CDC SDS) and Noonan standards (height-NS SDS). Results: The pretreatment chronological age was 10.3 +/- 3.5 years. Height-CDC SDS and height-NS SDS were -3.1 +/- 0.7 and -0.5 +/- 0.6, respectively. PTPN11+ patients had a better growth response than PTPN11- patients. GV SDS increased from -1.2 +/- 1.8 to 3.1 +/- 2.8 after the first year of therapy in PTPN11+ patients, and from -1.9 +/- 2.6 to -0.1 +/- 2.6 in PTPN11- patients. The gain in height-CDC SDS during the first year was higher in PTPN11+ than PTPN11- (0.6 +/- 0.4 vs. 0.1 +/- 0.2, p = 0.008). Similarly, the gain was observed in height-NS SDS (0.6 +/- 0.3 vs. 0.2 +/- 0.2, respectively, p < 0.001). Among the patients that reached adult height (n = 17), AH-CDC SDS and AH-NS SDS were -2.1 +/- 0.7 and 0.7 +/- 0.8, respectively. The total increase in height SDS was 1.3 +/- 0.7 and 1.5 +/- 0.6 for normal and NS standards, respectively. Conclusions: This study supports the advantage of rhGH therapy on adult height in PTPN11+ patients. In comparison, PTPN11- patients showed a poor response to rhGH. However, this PTPN11- group was small, preventing an adequate comparison among different genotypes and no guarantee of response to therapy in genes besides PTPN11. (C) 2019 S. Karger AG, Basel
conferenceObject Genetic Evaluation of Syndromic Short Stature Children Born Small for Gestational Age(2018) HOMMA, T.; FREIRE, B.; HONJO, R.; DAUBER, A.; FUNARI, M.; LERARIO, A.; ARNHOLD, I.; CANTON, A.; SUGAYAMA, S.; BERTOLA, D.; KIM, C.; MALAQUIAS, A.; JORGE, A.conferenceObject Genetic Investigation of Children with Syndromic Prenatal Onset Short Stature(2018) HOMMA, Thais; FREIRE, Bruna; RONJO, Rachel; DAUBER, Andrew; FUNARI, Mariana; LERARIO, Antonio; ARNHOLD, Ivo; CANTON, Ana; SUGAYAMA, Sofia; BERTOLA, Debora; KIM, Chong; MALAQUIAS, Alexsandra; JORGE, AlexanderconferenceObject GROWTH HORMONE (GH) THERAPY IMPROVES ADULT HEIGHT IN CHILDREN WITH NOONAN SYNDROME AND IDENTIFIED MUTATIONS IN PTPN11 GENE(2017) NORONHA, Renata M.; HOMMA, Thais K.; SOUZA, Thaiana T.; FUNARI, Mariana; PEREIRA, Alexandre C.; BERTOLA, Debora; JORGE, Alexander; MALAQUIAS, Alexsandra C.conferenceObject GENOMIC APPROACHES TO INVESTIGATE CHILDREN BORN SMALL FOR GESTATIONAL AGE (SGA) WITHOUT CATCH UP-GROWTH(2017) HOMMA, Thais K.; FREIRE, Bruna; FUNARI, Mariana; MALAQUIAS, Alexsandra; RONJO, Rachel; VASQUES, Gabriela; CANTON, Ana; KIM, Chong; BERTOLA, Debora; JORGE, AlexanderconferenceObject The Metabolic Profile Associated with RASopathies(2018) NORONHA, Renata; HOMMA, Thais; MORAES, Michelle; ALBUQUERQUE, Edoarda; FUNARI, Mariana; PEREIRA, Alexandre; VILLARES, Sandra; BERTOLA, Debora; JORGE, Alexander; MALAQUIAS, Alexsandra