Percorrer por autor "Soares, Gabriela"
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- Avanços no diagnóstico das doenças mitocondriais através da sequenciação de nova geraçãoPublication . Célia, Nogueira; Pereira, Cristina; Silva, Lisbeth; Encarnação, Marisa; Teles, Elisa Leão; Rodrigues, Esmeralda; Campos, Teresa; Janeiro, Patrícia; Gaspar, Ana; Soares, Gabriela; Bandeira, Anabela; Martins, Esmeralda; Magalhães, Marina; Santos, Helena; Vieira, Luís; Vilarinho, LauraO recente desenvolvimento da tecnologia de sequenciação de nova geração (NGS) revolucionou o diagnóstico molecular das doenças genéticas raras, de difícil diagnóstico, tais como as doenças mitocondriais. O estudo destas patologias foi implementado em 1993 pelo nosso grupo e até à data foram investigados mais de 2500 doentes portugueses. Muitos destes doentes ainda não dispõem de diagnóstico molecular, pelo que foi desenvolvida uma estratégia de NGS para a identificação da mutação causal. A sequenciação de um painel de 209 genes nucleares associados a doenças mitocondriais e do DNA mitocondrial completo por NGS, foi realizada num sequenciador MiSeq (Illumina). O estudo de 145 doentes permitiu identificar 41 mutações causais e caraterizar 35 doentes. Esta investigação contribuiu para esclarecer a etiologia molecular destes doentes (35/145; 24%), ii) alargar o espetro mutacional destas patologias e, iii) oferecer um aconselhamento genético e um eventual diagnóstico pré-natal aos casais em risco. O desenvolvimento de um painel, específico para estas patologias, tem um caráter inovador e reforça o nosso Centro como laboratório nacional para o estudo e investigação de doenças mitocondriais.
- Chromosome 1p36 deletion syndrome: a report on 4 casesPublication . Candeias, Cristina; Mota Freitas, Manuela; Ribeiro, Joana; Oliveira, Fernanda Paula; Aguiar, Joaquim; Oliva Teles, Natália; Soares, Gabriela; Carrilho, Inês; Martins, Márcia; Correia, Hildeberto; Fonseca Silva, Maria da LuzChromosome 1p36 deletion syndrome (MIM #607872) was first described in 1997 by Shapira et al. This condition is compatible with a monosomy of the 1p36 band in the distal region of the short arm of chromosome 1 and is the most common terminal deletion in humans, with an estimated prevalence of approximately 1 in 5,000 live births. This constitutional deletion is associated with mental retardation, developmental delay, seizures, hypotonia and heart defects. The syndrome is also characterized by several distinct dysmorphic features, including large anterior fontanels, microcephaly, brachycephaly, deep-set eyes, flat nose and nasal bridge, and pointed chin. The 1p36 band is not very clearly visible using classical cytogenetics, and it is therefore difficult to detect these deletions in banded karyotypes. Fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) analysis have increasingly been used, in addition to classical cytogenetic analysis, in children with mental retardation in order to identify this chromosomal abnormality. The authors present four patients between 1 month and 14 years of age with apparently normal karyotypes. Using molecular cytogenetic techniques, all cases showed a “pure” 1p36 deletion: three were detected by FISH (CEB108/T7, located at 1p36.3, Vysis) and are “de novo”; the fourth was detected by MLPA (P036 and P070, MRC Holland) analysis, and its origin is still unknown. The phenotypes of these patients are described and compared with other cases having this syndrome, described in the literature. We also emphasize the importance of good clinical characterization in order to establish the best cytogenetic strategy to assure accurate diagnosis.
- Co-segregation of trichorhinophalangeal syndrome with a t(8;13)(q23.3;q21.31) familial translocation that appears to increase TRPS1 gene expressionPublication . David, Dezső; Marques, Bárbara; Ferreira, Cristina; Araújo, Carlos; Vieira, Luís; Soares, Gabriela; Dias, Cristina; Pinto, MaximinaTrichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5’ end of TRPS1. Based on the additional abnormalities observed exclusively in the index patient that are mainly compatible with clinical features of TRPS, her phenotype was defined as expanded TRPS I including brain malformations and intellectual disability. Initial analyses did not reveal any genetic defect affecting TRPS1 or any genomic alteration within the breakpoint regions or elsewhere in the genome. The pathogenic chromosome 8q23.3 breakpoint is at position g.116,768,309_116,768,310 within a transposon type I element, 87 kb from the TRPS1 5’ end. The 13q21.31 breakpoint is within a tandem repeat region at position g.65,101,509_65,101,510 (genome assembly GRCh37/hg19). This breakpoint is flanked by protocadherin 9 (PCDH9) and protocadherin 20 (PCDH20). As an outcome of the translocation, an evolutionarily conserved non-coding VISTA enhancer element from 13q21.31 is placed within the TRPS1 5’ region, 1,294 bp from the breakpoint. The increased expression of TRPS1 found by three independent methods is most probably translocation allele derived and driven by the translocated enhancer element. The index patient’s expanded phenotype presumably involves the epithelial-to-mesenchymal transition pathway that may be due to TRPS1 overexpression. Together, these findings support that the reported translocation associated phenotypes are “cis-ruption” and TRPS1 overexpression related, the latter most probably caused by the novel enhancer element in the TRPS1 5’ region.
- A "de novo" inv dup del(6q) - a case reportPublication . Mota Freitas, Manuela; Candeias, Cristina; Oliva Teles, Natália; Soares, Gabriela; Tkachenko, Nataliya; Marques, Bárbara; Correia, Hildeberto; Fonseca da Silva, Maria da Luz
- Defeitos Genéticos das Doenças Mitocondriais: Abordagem por Sequenciação de Nova GeraçãoPublication . Nogueira, Célia; Pereira, Cristina; Silva, Lisbeth; Vieira, Luis; Leão Teles, Elisa; Rodrigues, Esmeralda; Campos, Teresa; Janeiro, Patricia; Costa, Claúdia; Gaspar, Ana; Soares, Gabriela; Bandeira, Anabela; Martins, Esmeralda; Santos, Helena; Vilarinho, LauraObjetivos:O objetivo deste projeto de investigação é desenvolver uma estratégia de sequenciação de nova geração para a identificação das alterações genéticas em doentes suspeitos de doenças mitocondriais sem caracterização molecular.
- Diagnóstico das Doenças Mitocondriais por Sequenciação de Nova GeraçãoPublication . Nogueira, Célia; Pereira, Cristina; Silva, Lisbeth; Rodrigues, Esmeralda; Janeiro, Patricia; Sequeira, Sílvia; Santos, Helena; Martins, Esmeralda; Vilarinho, Laura; Vieira, Luis; Leão Teles, Elisa; Campos, Teresa; Costa, Cláudia; Gaspar, Ana; Dupont, Juliette; Soares, Gabriela; Bandeira, Anabela; Magalhães, Marina; Vieira, José PedroIntrodução e objetivos: As doenças mitocondriais constituem um importante grupo de doenças metabólicas de expressão clínica heterogénea, para as quais não existe uma terapia eficaz. Estas patologias podem ser causadas por defeitos genéticos quer no genoma mitocondrial, quer no nuclear. A sequenciação de nova geração (NGS) revolucionou o diagnóstico molecular destas doenças, uma vez que tem capacidade de gerar uma enorme quantidade de dados num curto espaço de tempo a um custo acessível. O objetivo deste estudo [Financiado pela FCT (PTDC/DTP-PIC/2220/2014) e pelo Norte 2020 (NORTE-01-0246-FEDER-000014)] é desenvolver uma estratégia de NGS para permitir o diagnóstico genético de doentes suspeitos de doenças mitocondriais.
- Koolen-de Vries syndrome – National Case Series with clinical and molecular characterizationPublication . Soares, Marta P.; Rodrigues, Márcia; Dupont, Juliette; Medeira, Ana; Freixo, João; Nunes, Sofia; Cordeiro, Isabel; Travessa, André; Soares, Gabriela; Fortuna, Ana; Ramos, Fabiana; Sá, Joaquim; Rocha, Susana; Figueiredo, Cristina; Mendonça, Carla; Tapadinhas, Fernando; Silveira-Santos, Rosário; Custódio, Sónia; Barreta, Ana; Serafim, Sílvia; Correia, Hildeberto; Val, Mariana; Carreira, Isabel M.; Rendeiro, Paula; Sousa, Ana; Sousa, Ana BertaIntroduction: Koolen-de Vries Syndrome (KdVS) is a rare genetic condition, caused by a 17q21.31 microdeletion, or a pathogenic variant in KANSL1 gene. The clinical picture includes developmental delay (DD)/intellectual disability (ID) with expressive language particularly impaired, dysmorphisms, neonatal hypotonia, and friendly behaviour. Aim: To characterize at the molecular and clinical levels all patients in Portugal diagnosed with KdVS.
- McArdle disease: mutational spectrum of Portuguese patientsPublication . Rocha, Hugo; Lopes, Altina; Soares, Gabriela; Negrão, Luis; Coelho, Teresa; Chorão, Rui; Lourenço, Teresa; Vilarinho, LauraMcArdle disease or Glycogen Storage Disease type V (GSD V; myophosphorylase deficiency; MIM 232600) its an inborn error of glycogen metabolism, caused by a deficiency in muscle specific isoform of glycogen phosphorylase. This metabolic myopathy is characterised by exercise intolerance, myalgia, cramps and episodic myoglobinuria, symptoms that usually appear during the second or third decade of life. The diagnosis was typically made in muscle biopsy by histological analysis (demonstration of subsarcolemmal glycogen deposits and negative histochemical stain for phosphorylase) and/or measurement of muscle phosphorylase activity. Although since 1984, when the gene of muscle isoform of phosphorylase (myophosphorylase) was cloned and assigned to chromosome 11 (11q13), molecular genetics analysis has been more and more used to confirm the clinical diagnosis. Until now, 146 pathogenic mutations have been described (according to HGMDTM) including nonsense, missense and framshift mutations. High genetic heterogeneity is a hallmark of McArdle disease with a very frequent common mutation among Caucasian populations – R49X (present in about 60% of the mutated alleles) – and several rare mutations, without a clear genotype/phenotype correlation. The authors will present molecular data from the characterisation of 53 Portuguese patients, from 42 families, with McArdle disease. Our results reveal the presence of the R49X mutation in 60 of the alleles (57%), in accordance to what has been described to other Caucasian populations, being identified a total of 15 different mutations were identified. These results allowed in many cases the diagnosis without the need of a muscle biopsy, but also provide valuable information for genetic counselling and to increase the knowledge about the molecular pathology of this disorder.
- Mitochondrial disorders: insights into diagnosis and management in the new era of genomic medicinePublication . Nogueira, Célia; Vilarinho, Laura; Pereira, Cristina; Silva, Lisbeth; Vieira, Luís; Leão Teles, Elisa; Rodrigues, Esmeralda; Campos, Teresa; Janeiro, Patricia; Costa, Cláudia; Gaspar, Ana; Dupont, Juliette; Soares, Gabriela; Bandeira, Anabela; Martins, Esmeralda; Magalhães, Marina; Santos, HelenaObjectives: The overall aim of our research project was to develop a Next Generation Sequencing strategy to identify nuclear disease causing-mutations in patients suspicious of mitochondrial disorders but without molecular etiology.
- Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian PeninsulaPublication . Mangas, Mariana; Nogueira, Célia; Prata, Maria João; Lacerda, Lúcia; Coll, M.J.; Soares, Gabriela; Ribeiro, Gil; Amaral, Olga; Ferreira, Célia; Alves, C.; Coutinho, Maria Francisca; Alves, SandraMucopolysaccharidosis type IIIB (Sanfilippo B disease) is a rare autosomal recessive disorder caused by defective alpha-N-acetylglucosaminidase (NAGLU). We examined the NAGLU gene in 11 MPS IIIB Portuguese patients, having identified five novel (M1K, W147X, G304V, S522P, and R533X) and four previously reported mutations (W168X, R234C, R565W and R643C). R234C attained the high prevalence of 32% of the mutated alleles. Because R234C had already been reported to be common in Spanish patients, a haplotypic analysis was conducted to address the question of its origin in the Iberian Peninsula. Three neutral markers were studied that allowed for the identification of the probable founder haplotype (174-234-G) on which R234C arose. The sharing of the ancestral haplotype by Portuguese and Spanish patients clearly implied a common origin of the mutation in Iberia, through an event that was inferred to have been rather recent. Therefore, the reconstructed history of R234C explains the high incidence of the mutation in Iberian patients with Sanfilippo B disease.