ROBERTA LELIS DUTRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- A Possible Role of Different PTPN Genes in Immune Regulation(2012) QUAIO, C. R. D. C.; DUTRA, R. L.; BRASIL, A. S.; PEREIRA, A. C.; KIM, C. A.; BERTOLA, D. R.
- Cytogenomic delineation and clinical follow-up of 10 Brazilian patients with Pallister-Killian syndrome(2015) COSTA, Larissa Sampaio de Athayde; ZANDONA-TEIXEIRA, Aline C.; MONTENEGRO, Marilia M.; DIAS, Alexandre T.; DUTRA, Roberta L.; HONJO, Rachel S.; BERTOLA, Debora R.; KULIKOWSKI, Leslie D.; KIM, Chong A.Background: Pallister-Killian syndrome (PKS) is a sporadic genetic disorder caused by the presence of a tissue-specific mosaicism for isochromosome 12p - i(12) (p10) and is characterized by facial dysmorphism including coarse facies, upslanting palpebral fissures, bitemporal alopecia, pigmentary skin anomalies, developmental delay, hypotonia and seizures. Although typical clinical features of PKS commonly exist, clinicians often do not raise the possibility of this diagnosis. Results: We reviewed the medical records of 10 patients with confirmed PKS followed in our service (since 1990 to 2015). Age at diagnosis varied from prenatal to 3 years and clinical features were consistent with those described in the literature. In all patients, peripheral blood karyotypes were normal and cytogenomic study was performed in order to confirm the diagnosis. Three of these patients had PKS diagnosis confirmed by buccal smear MLPA. Conclusion: An early conclusion from our results demonstrated that MLPA on buccal smears is a good and non-invasive method to detect extra copies of 12p and should be considered as the first exam, before a skin biopsy for a fibroblast karyotype is performed.
- Post-mortem cytogenomic investigations in patients with congenital malformations(2016) DIAS, Alexandre Torchio; ZANARDO, Evelin Aline; DUTRA, Roberta Lelis; PIAZZON, Flavia Balbo; NOVO-FILHO, Gil Monteiro; MONTENEGRO, Marilia Moreira; NASCIMENTO, Amom Mendes; ROCHA, Mariana; MADIA, Fabricia Andreia Rosa; COSTA, Thais Virginia Moura Machado; MILANI, Cintia; SCHULTZ, Regina; GONCALVES, Fernanda Toledo; FRIDMAN, Cintia; YAMAMOTO, Guilherme Lopes; BERTOLA, Debora Romeo; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciCongenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), micro satellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin -embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p1132); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C > G (c.746C > G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.
- Williams-Beuren Syndrome: A Clinical Study of 55 Brazilian Patients and the Diagnostic Use of MLPA(2015) HONJO, Rachel Sayuri; DUTRA, Roberta Lelis; FURUSAWA, Erika Arai; ZANARDO, Evelin Aline; COSTA, Larissa Sampaio de Athayde; KULIKOWSKI, Leslie Domenici; BERTOLA, Debora Romeo; KIM, Chong AeWilliams-Beuren syndrome (WBS) is a genetic disease caused by a microdeletion in the 7q11.23 region. It is characterized by congenital heart disease, mainly supravalvular aortic stenosis, mental retardation, mild short stature, facial dysmorphisms, and variable abnormalities in different systems. Objectives. To report the clinical findings of 55 Brazilian patients confirmed by multiplex ligation-dependent probe amplification (MLPA). Methods. Patients were followed up for 4 years at the Genetics Unit of the Instituto da Crianca of the Hospital das Clinicas, FMUSP, Brazil. A kit specific for WBS was used to detect the 7q11.23 microdeletion. Results. Two patients with negative FISH results had positive MLPA results for WBS. The characteristics of the patients with the deletion were as follows: typical WBS facies (98.2%), neuropsychomotor delay (98.2%), hypersocial behavior (94.5%), hyperacusis (94.5%), and congenital heart disease (81.8%). Conclusions. MLPA was effective in detecting the microdeletion in the 7q11.23 region to confirm the diagnosis of WBS. MLPA was also able to confirm the diagnosis of WBS in two patients with typical clinical characteristics but negative FISH results. Thus, MLPA is a promising method in the diagnostic investigation of WBS. WBS is a multisystemic disorder and therefore requires multidisciplinary care and specific follow-up to prevent complications.
- Williams-Beuren Syndrome: A Clinical Study of 55 Brazilian Patients and the Diagnostic Use of MLPA (vol 2015, 903175, 2015)(2015) HONJO, Rachel Sayuri; DUTRA, Roberta Lelis; FURUSAWA, Erika Arai; ZANARDO, Evelin Aline; COSTA, Larissa Sampaio de Athayde; KULIKOWSKI, Leslie Domenici; BERTOLA, Debora Romeo; KIM, Chong Ae
- Assessment of Intellectual and Visuo-Spatial Abilities in Children and Adults with Williams Syndrome(2013) NUNES, M. M.; HONJO, R. S.; DUTRA, R. L.; AMARAL, V. S.; AMARAL, V. A. S.; OH, H. K.; BERTOLA, D. R.; ALBANO, L. M. J.; JR, F. B. Assumpcao; KIM, C. A.; V, M. C. T. TeixeiraThe Williams-Beuren syndrome (SWB), also known as Williams syndrome, is a contiguous gene deletion of the region 7q.11.23. The main clinical characteristics are typical faces, supravalvular aortic stenosis, failure to thrive, short stature, transient neonatal hypercalcemia, delayed language, friendly personality, hyperacusis and intellectual disability. The diagnosis of SWB is confirmed by the detection of micro deletion by different techniques of molecular cytogenetics, FISH, MLPA or polymorphic markers. This study assessed the verbal intelligence quotient (IQ) and performance and visuo-spatial skills in children and adults with WBS. The composed group was of 31 WBS patients (19 M and 12 F), whose ages ranged from 9 to 26 years (M 14.45 y). All patients had the diagnosis confirmed molecularly. The tests used were the WISC-III, WAIS-III and Rey-Osterrieth Complex Figure Test. The results indicated a total IQ ranged from 51 to 86 (M 63): 22 with mild intellectual disability, 4 with moderate intellectual disability, 4 borderlines and 1 below the normal media. All patients had marked visual-spatial deficits. The results suggest nonverbal reasoning, visuo-spatial perception, spatial representation, working memory, motor planning and executive functions are very affected in this group.
- Detection of deletions at 7q11.23 in Williams-Beuren syndrome by polymorphic markers(2011) DUTRA, Roberta Lelis; PIERI, Patricia de Campos; TEIXEIRA, Ana Carolina Dias; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeINTRODUCTION: Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis, mental retardation, overfriendliness, and ocular and renal abnormalities comprise typical symptoms in WBS. Although fluorescence in situ hybridization is widely used for diagnostic confirmation, microsatellite DNA markers are considered highly informative and easily manageable. OBJECTIVES: This study aimed to test the microsatellite markers for the diagnosis of Williams-Beuren syndrome, to determine the size and parental origin of microdeletion, compare the clinical characteristics between patients with different sizes of the deletion and parental origin. METHODS: We studied 97 patients with clinical diagnosis of Williams-Beuren syndrome using five microsatellite markers: D7S1870, D7S489, D7S613, D7S2476 and D7S489_A. RESULTS AND DISCUSSION: Using five markers together, the result was informative in all patients. The most informative marker was D7S1870 (78.4%), followed by D7S613 (75.3%), D7S489 (70.1%) and D7S2476 (62.9%). The microdeletion was present in 84 (86.6%) patients and absent in 13 (13.4%) patients. Maternal deletions were found in 52.4% of patients and paternal deletions in 47.6% of patients. The observed size of deletions was 1.55 Mb in 76/84 patients (90.5%) and 1.84 Mb in 8/84 patients (9.5%). SVAS as well as ocular and urinary abnormalities were more frequent in the patients with a deletion. There were no clinical differences in relation to either the size or parental origin of the deletion. CONCLUSION: Using these five selected microsatellite markers was informative in all patients, thus can be considered an alternative method for molecular diagnosis in Williams-Beuren syndrome.