FERNANDA DE AZEVEDO CORREA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
conferenceObject NOVEL LZTR1 GENE VARIANTS ASSOCIATED TO NOONAN SYNDROME AND GROWTH HORMONE DEFICIENCY(2017) NAKAGUMA, Marilena; JORGE, Alexander A. L.; MARIANA, Funari F. A.; ANTONIO, Lerario M.; FERNANDA, Correa A.; LUCIANI, Carvalho R. S.; BERENICE, Mendonca B.; ARNHOLD, Ivo J.- Pathogenic copy number variants in patients with congenital hypopituitarism associated with complex phenotypes(2018) CORREA, Fernanda A.; JORGE, Alexander A. L.; NAKAGUMA, Marilena; CANTON, Ana P. M.; COSTA, Silvia S.; FUNARI, Mariana F.; LERARIO, Antonio M.; FRANCA, Marcela M.; CARVALHO, Luciani R.; KREPISCHI, Ana C. V.; ARNHOLD, Ivo J. P.; ROSENBERG, Carla; MENDONCA, Berenice B.ObjectivesThe aetiology of congenital hypopituitarism (CH) is unknown in most patients. Rare copy number variants (CNVs) have been implicated as the cause of genetic syndromes with previously unknown aetiology. Our aim was to study the presence of CNVs and their pathogenicity in patients with idiopathic CH associated with complex phenotypes. Design and PatientsWe selected 39 patients with syndromic CH for array-based comparative genomic hybridization (aCGH). Patients with pathogenic CNVs were also evaluated by whole exome sequencing. ResultsTwenty rare CNVs were detected in 19 patients. Among the identified rare CNVs, six were classified as benign, eleven as variants of uncertain clinical significance (VUS) and four as pathogenic. The three patients with pathogenic CNVs had combined pituitary hormone deficiencies, and the associated complex phenotypes were intellectual disabilities: trichorhinophalangeal type I syndrome (TRPS1) and developmental delay/intellectual disability with cardiac malformation, respectively. Patient one has a de novo 1.6-Mb deletion located at chromosome 3q13.31q13.32, which overlaps with the region of the 3q13.31 deletion syndrome. Patient two has a 10.5-Mb de novo deletion at 8q23.1q24.11, encompassing the TRPS1 gene; his phenotype is compatible with TRPS1. Patient three carries a chromosome translocation t(2p24.3;4q35.1) resulting in two terminal alterations: a 2p25.3p24.3 duplication of 14.7Mb and a 4-Mb deletion at 4q35.1q35.2. ConclusionsCopy number variants explained the phenotype in 8% of patients with hypopituitarism and additional complex phenotypes. This suggests that chromosomal alterations are an important contributor to syndromic hypopituitarism.
- Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR(2019) NAKAGUMA, Marilena; CORREA, Fernanda A.; SANTANA, Lucas S.; BENEDETTI, Anna F. F.; V, Ricardo Perez; HUAYLLAS, Martha K. P.; MIRAS, Mirta B.; FUNARI, Mariana F. A.; LERARIO, Antonio M.; MENDONCA, Berenice B.; CARVALHO, Luciani R. S.; JORGE, Alexander A. L.; ARNHOLD, Ivo J. P.Aim: Congenital hypopituitarism has an incidence of 1:3500-10,000 births and is defined by the impaired production of pituitary hormones. Early diagnosis has an impact on management and genetic counselling. The clinical and genetic heterogeneity of hypopituitarism poses difficulties to select the order of genes to analyse. The objective of our study is to screen hypopituitarism genes (candidate and previously related genes) simultaneously using a target gene panel in patients with congenital hypopituitarism. Methods: Screening of 117 subjects with congenital hypopituitarism for pathogenic variants in 26 genes associated with congenital hypopituitarism by massively parallel sequencing using a customized target gene panel. Results: We found three novel pathogenic variants in OTX2 c.295C>T:p.Gln99*, GLI2 c.1681G>T:p.Glu561* and GHRHR c.820_821insC:p.Asp274Alafs*113, and the previously reported variants in GHRHR c.57+1G>A and PROP1 [c.301_302delAG];(c.109+1G>A]. Conclusions: Our results indicate that a custom-designed panel is an efficient method to screen simultaneously variants of biological and clinical relevance for congenital GH deficiency. A genetic diagnosis was possible in 5 out of 117 (4%) patients of our cohort. We identified three novel pathogenic variants in GHRHR, OTX2 and GLI2 expanding the spectrum of variants associated with congenital hypopituitarism.
conferenceObject A novel mutation in PROP1 c.109+1G > A identified by target gene panel in patients with congenital growth hormone deficiency(2018) NAKAGUMA, M.; JORGE, A. A. L.; FUNARI, M. F. A.; LERARIO, A. M.; CORREA, F. A.; CARVALHO, L. R. S.; ARNHOLD, I. J. P.conferenceObject Probably Pathogenic Variants in New Candidate Genes in Patients with Pituitary Stalk Interruption Syndrome (PSIS) Revealed by Whole-Exome Sequencing(2019) CORREA, F. A.; NAKAGUMA, M.; JORGE, A. A. L.; FUNARI, M. F. A.; LERARIO, A. M.; CARVALHO, L. R. S.; ARNHOLD, I. J. P.; MENDONCA, B. B.conferenceObject Genetic Diagnosis of Congenital Growth Hormone Deficiency by Massive Parallel Sequencing Using a Target Gene Panel(2016) NAKAGUMA, Marilena; JORGE, Alexander Augusto de Lima; FUNARI, Mariana Ferreira de Assis; LERARIO, Antonio Marcondes; CORREAA, Fernanda de Azevedo; CARVALHOA, Luciani Renata Silveira de; MENDONCA, Berenice Bilharinho de; ARNHOLD, Ivo Jorge Prado