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
163 resultados
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conferenceObject Genetic profile of Brazilian patients with nucleotide excision repair deficiency(2019) CASTRO, L. P.; MUNFORD, V.; ANTONIO, T. S.; EZQUINA, S.; MOURA, L.; VALLE, F. F.; BERTOLA, D. R.; LAJUS, T. B. P.; CAMPOS-DO-CARMO, G.; FERREIRA, P. S.; ROCHA, L.; MAIA, M. H. T.; DONATI, A.; ASHTON-PROLLA, P.; SOUTO, R.; CHAIBUB, S. C.; MENCK, C. F.- Mucopolysaccharidosis Type IVA: Evidence of Primary and Secondary Central Nervous System Involvement(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; GOMY, Israel; BERTOLA, Debora Romeo; KIM, Chong AeMucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (+/- 5.7) and the mean onset of symptoms was 11.5 months (+/- 6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes. (c) 2014 Wiley Periodicals, Inc.
- Nationwide questionnaire data of 229 Williams-Beuren syndrome patients using WhatsApp tool(2021) PIRES, Lucas Vieira Lacerda; RIBEIRO, Rogerio Lemos; SOUSA, Adriana Modesto de; LINNENKAMP, Bianca Domit Werner; PONTES, Sue Ellen; TEIXEIRA, Maria Cristina Triguero Veloz; BEFI-LOPES, Debora Maria; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeBackground: Williams-Beuren syndrome is a multisystemic disorder caused by a microdeletion of the 7q 11.23 region. Although familial cases with autosomal dominant inheritance have been reported, the vast majority are sporadic. Objective: To investigate the main complaints and clinical findings of patients with Williams-Beuren syndrome. Methods: A total of 757 parents of patients registered in the Brazilian Association of Williams-Beuren Syndrome (ABSW) received a questionnaire via WhatsApp from March to July 2017. Results: In total, 229 parents answered the survey. Age of diagnosis ranged from 2 days to 34 years (median: 3 years). The main clinical findings reported by the parents were abdominal colic (83.3%), failu re to thrive (71.5%), feeding difficulty in the first year (68.9%), otitis (56.6%), urinary tract infections (31.9%), precocious puberty (27.1%) and scoliosis (15.9%). Cardiac defects were present in 66% of patients, and the most frequent defect was supravalvular aortic stenosis (36%). Arterial hypertension was reported in 23%. Hypercalcemia was reported in 10.5% of patients, mainly during the first year of life. Hyperacusis and hypersociability were common complaints (both present in 89%). Other behavioral and neuropsychiatric symptoms reported by the parents included attention deficit (89%), anger crises (83%), excessive fear (66%), depression (64%), anxiety (67%) and hypersexuality(33%).The most common complaints were hypersensitivity to sounds, talkative personality, emotional dependence and learning difficulties. In 98.3%, the parents denied family history. Conclusions: Williams-Beuren syndrome requires close follow-up with different medical specialties due to their variable clinical comorbidities, including language and school learning difficulties, behavioral and psychiatric problems.
- Microdeletion 11q13.1.q13.2 in a Patient Presenting with Developmental Delay, Facial Dysmorphism, and Esophageal Atresia: Possible Role of the GSTP1 Gene in Esophagus Malformation(2013) ALMEIDA, Tatiana Ferreira de; BERTOLA, Debora RomeoBACKGROUND: Esophageal atresia is a major congenital malformation characterized by a complete interruption of the esophageal continuity. It is frequently observed in associations and syndromes. As an isolated finding, it has a multifactorial etiology whose genetic factors are poorly known. Recently, the GST family, especially the GSTM1 null genotype (but not the GSTP1 polymorphism I105V), has been associated with esophageal atresia. These enzymes play a role in phase II detoxification of xenobiotics. Here we present the clinical and molecular findings observed in a patient suggesting that the loss of the GSTP1 allele might predispose to this malformation. CASE: We describe a patient presenting with esophageal atresia associated with developmental delay and facial dysmorphism, whose mother used tobacco and alcohol during the first 2 months of her pregnancy. Microdeletion/microduplication analysis was performed using comparative genomic hybridization and a 180K Agilent array. It detected a de novo 2 Mb chromosome 11q13.1.q13.2 deletion. CONCLUSION: The deleted chromosomal segment includes the GSTP1 gene. We hypothesize that the deletion of one GSTP1 allele (an isoform highly expressed in embryonic tissues), associated with specific environmental factors, such as tobacco and alcohol, could cause the esophageal atresia observed in our patient. Birth Defects Research (Part A) 97:463-466, 2013. (c) 2013 Wiley Periodicals, Inc.
- Cross-national harmonization of cognitive measures across HRS HCAP (USA) and LASI-DAD (India)(2022) VONK, Jet M. J.; GROSS, Alden L.; ZAMMIT, Andrea R.; BERTOLA, Laiss; AVILA, Justina F.; JUTTEN, Roos J.; GAYNOR, Leslie S.; SUEMOTO, Claudia K.; KOBAYASHI, Lindsay C.; O'CONNELL, Megan E.; ELUGBADEBO, Olufisayo; AMOFA, Priscilla A.; STAFFARONI, Adam M.; RENTERIA, Miguel Arce; TURNEY, Indira C.; JONES, Richard N.; MANLY, Jennifer J.; LEE, Jinkook; ZAHODNE, Laura B.Background As global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD). Methods Data for 3,496 HRS HCAP (>= 65 years) and 3,152 LASI-DAD (>= 60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision. Results CFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample. Conclusions Harmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.
- Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion(2014) MOYSES-OLIVEIRA, Mariana; MANCINI, Tatiane I.; TAKENO, Sylvia S.; RODRIGUES, Andressa D. S.; BACHEGA, Tania A. S. S.; BERTOLA, Debora; MELARAGNO, Maria IsabelCryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including CYP21A2,TNXB and MSH5. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes CYP21A1P and C4B. CYP21A2 sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the CYP21A2 gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes TNXB and MSH5, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family. (C) 2014 S. Karger AG, Basel
- Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients(2022) LLERENA JR., Juan; KIM, Chong Ae; FANO, Virginia; ROSSELLI, Pablo; COLLETT-SOLBERG, Paulo Ferrez; MEDEIROS, Paula Frassinetti Vasconcelos de; PINO, Mariana del; BERTOLA, Debora; LOURENCO, Charles Marques; CAVALCANTI, Denise Pontes; FELIX, Temis Maria; ROSA-BELLAS, Antonio; ROSSI, Norma Teresa; CORTES, Fanny; ABREU, Flavia; CAVALCANTI, Nicolette; RUZ, Maria Cecilia Hervias; BARATELA, WagnerBackground Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries. Methods Latin American experts (from Argentina, Brazil, Chile and Colombia) particiated of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia. Results Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included. Conclusions This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.
- Multiple, diffuse schwannomas in a RASopathy phenotype patient with germline KRAS mutation: a causal relationship?(2012) BERTOLA, D. R.; PEREIRA, A. C.; BRASIL, A. S.; SUZUKI, L.; LEITE, C.; FALZONI, R.; TANNURI, U.; POPLAWSKI, A. B.; JANOWSKI, K. M.; KIM, C. A.; MESSIAEN, L. M.
- Stuve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects(2016) BERTOLA, Debora Romeo; HONJO, Rachel S.; BARATELA, Wagner A. R.Stuve-Wiedemann syndrome is a rare autosomal recessive disorder characterized by bowed long bones, joint restrictions, dysautonomia, and respiratory and feeding difficulties, leading to death in the neonatal period and infancy in several occasions. Since the first cases in 1971, much has been learned about this condition, including its molecular basis - mutations in the leukemia inhibitory factor receptor gene (LIFR) -, natural history and management possibilities. This review aims to highlight the clinical aspects, radiological features, molecular findings, and management strategies in Stuve-Wiedemann syndrome. (C) 2016 S. Karger AG, Basel
- 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.