EDOARDA VASCO DE ALBUQUERQUE ALBUQUERQUE
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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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.
- 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.
- Genetic investigation of patients with tall stature(2020) ALBUQUERQUE, Edoarda Vasco de Albuquerque; FUNARI, Mariana Ferreira de Assis; QUEDAS, Elisangela Pereira de Souza; KAWAHIRA, Rachel Sayuri Honjo; JALLAD, Raquel Soares; HOMMA, Thais Kataoka; MARTIN, Regina Matsunaga; BRITO, Vinicius Nahime; MALAQUIAS, Alexsandra Christianne; LERARIO, Antonio Marcondes; ROSENBERG, Carla; KREPISCHI, Ana Cristina Victorino; KIM, Chong Ae; ARNHOLD, Ivo Jorge Prado; JORGE, Alexander Augusto de LimaContext: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.