Browsing by Author "Pedro, Sónia"
Now showing 1 - 10 of 22
Results Per Page
Sort Options
- A 1.77 Mb deletion in 3p26.3 encompassing CNTN6 and CNTN4 genes: case reportPublication . Brito, Filomena; Marques, Bárbara; Pedro, Sónia; Serafim, Silvia; Gonçalves, Rui; Freixo, João; Correia, HildebertoChromosome microarray analysis is a powerful diagnostic tool and is being used as a first-line approach to detect chromosome imbalances associated with intellectual disability, dysmorphic features and congenital abnormalities. This test enables the identification of new copy number variants (CNVs) and their association with new microdeletion/microduplication syndromes in patients previously without diagnosis. We report the case of a 7 year-old female with moderate intellectual disability, severe speech delay and auto and hetero aggressivity with a previous 45,XX,der(13;14)mat karyotype performed at a younger age. Affymetrix CytoScan 750K chromosome microarray analysis was performed detecting a 1.77 Mb deletion at 3p26.3, encompassing 2 OMIM genes, CNTN6 and CNTN4. These genes play an important role in the formation, maintenance, and plasticity of functional neuronal networks. Deletions or mutations in CNTN4 gene have been implicated in intellectual disability and learning disabilities. Disruptions or deletions in the CNTN6 gene have been associated with development delay and other neurodevelopmental disorders. The haploinsufficiency of these genes has been suggested to participate to the typical clinical features of 3p deletion syndrome. Nevertheless inheritance from a healthy parent has been reported, suggesting incomplete penetrance and variable phenotype for this CNV. We compare our patient with other similar reported cases, adding additional value to the phenotype-genotype correlation of deletions in this region.
- 15q11.2q13.1 interstitial gain in a fetus with an increased risk for T21: When classification and clinical outcome are divergentPublication . Serafim, Sílvia; Pedro, Sónia; Marques, Bárbara; Tarelho, Ana; Viegas, Mónica; Simão, Laurentino; Ferreira, Cristina; Carvalho, Inês; Cohen, Álvaro; Correia, HildebertoIntroduction: Copy number variants (CNV) of the 15q11.2q13.1 region are associated to recurrent microdeletion/microduplication syndromes in which the phenotype is dependent on the parental origin of the CNV. We report the case of a fetus from a healthy 39-year-old G6P3A2 woman, with an increased risk for trisomy 21 in the 1st trimester prenatal screening. Chromosomal microarray analysis (CMA) was requested and revealed a pathogenic duplication in which the outcome was dependent of the parental origin of the affected allele. Methods: DNA was extracted from a chorionic villus sample and CMA was performed using Cytoscan™ 750K. Parental follow-up studies to assess the origin of the CNV were performed. Results: The CMA profile revealed a male fetus with a 4,89 Mb interstitial gain in 15q11.2q13.1. CMA of the parents showed that the duplication was paternally inherited. Discussion: The detected CNV is a recurrent known microduplication and according to the American College of Medical Genetics and Genomics guidelines is classified as pathogenic. However the phenotype is dependent on the parental origin of the duplication. When it arises in the maternally allele it has a severe outcome with hypotonia, cognitive deficit, seizures, among others. If the CNV occurs in the paternal allele although some patients might show developmental delays and behavioral disturbances most cases are rarely symptomatic. In this case, CMA of both parents showed that the CNV identified in the fetus was paternally inherited. Although the CMA result did not explained the increased risk for T21 after determining the duplication had been inherited from the father it allowed the prediction of the most likely resulting phenotype for the fetus as a milder or even asymptomatic. Follow-up ultrasounds at gestation age of 17w+6d and echocardiogram at 21w+3d showed no structural abnormalities. The baby was born at 37w+5d with an Apgar index of 10/10/10, with no dysmorphic features or malformations, and a normal physical exam. This case illustrates that although the use of genetic tools using artificial intelligence and following determined guidelines can be helpful for the purpose of consistency and standardization on the classification we always need careful evaluation from a clinical laboratory geneticist on the context of each case. Additionally it also shows how critical parental testing can be, not only to assess recurrence risk but to provide the best possible tool to ascertain the outcoming phenotype and allow the best choices to the couple after genetic counselling.
- A 669Kb deletion in 17q23.2, encompassing TBX2 and TBX4 genes, in a girl with a moderate developmental delay without any other pertinent abnormalityPublication . Ferreira, Cristina; Marques, Bárbara; Pedro, Sónia; Serafim, Silvia; Amorim, Marta; Correia, HildebertoMicrodeletion of the 17q23.1-q23.2 region recently emerged as a syndrome (OMIM#613355) based in a small number of cases with a common phenotype including mild-to-moderate developmental delay, heart defects, microcephaly, postnatal grow retardation, and hand, foot, and limb abnormalities. All patients reported to date present mild to moderate developmental delay, in particular speech delay, and half of them hearing loss. The smallest overlapping region has approximately 2.2 Mb and includes the transcription factors TBX2 and TBX4 genes. These genes have been implicated in a number of developmental pathways, including those of the heart and limbs. The TBX4 gene is also associated with the autosomal dominant small patella syndrome (SPS, OMIM 147891). Here we report a 8 year-old girl with moderate developmental delay including learning disabilities. The test for Fragile X syndrome indicated an allele within the grey area (number of repeats ~50 CGG) inherited from her mother and probably not relevant. Affymetrix Cytoscan HD chromosome microarray analysis was performed and a 669 Kb interstitial deletion was detected at 17q23.2 region, encompassing only five OMIM genes: BCAS3, TBX2, TBX4, NACA2 and BRIP1. To our knowledge this is the smallest deletion described in this region. None of the genes present in the deleted region are known to be associated with developmental problems. We compare our patient with the other similar reported cases, in order to add some increased value to the phenotype-genotype correlation of deletions in this region.
- Actividade gripal em Portugal no Inverno de 2000/2001 - Análise antigénica e genética das estirpes de vírus influenzaPublication . Pechirra, Pedro; Rebelo-de-Andrade, Helena; Guiomar, Raquel; Ribeiro, Carlos; Coelho, Anabela; Pedro, Sónia; George, FranciscoAs infecções por vírus influenza são uma importante causa de morbilidade em todos os grupos etários e estão associados a uma elevada mortalidade nos idosos e nos indivíduos pertencentes a grupos de risco. No presente estudo analisaram-se os dados da vigilância epidemiológica da gripe durante o Inverno de 2000/2001. Os dados clínicos, epidemiológicos e virológicos referentes aos casos de síndroma gripal foram recolhidos através do Programa Nacional de Vigilância da Gripe que se desenvolve em colaboração com a Direcção Geral da Saúde e integra a informação obtida a partir das redes Médicos-Sentinela e Serviços de Urgência. A análise dos dados recolhidos mostram que, durante a época de Inverno de 2000/2001, a actividade gripal foi baixa, sendo o período epidémico curto e de pequena intensidade e duração. As taxas de incidência do síndrome gripal subiram acima da linha de base durante três semanas e não ultrapassaram os 74 casos por 100 000 habitantes. Os vírus influenza do tipo B foram predominantes, verificando-se a presença simultânea de vírus influenza tipo AH1 e AH3. A caracterização antigénica e genética das estirpes isoladas permitiu confirmar a semelhança entre estas estirpes virais e as estirpes vacinais e detectar a extensão dos drifts antigénicos. Saliente-se que apesar da maioria das estirpes de vírus influenza B serem idênticas antigenicamente à estirpe vacinal, a caracterização genética mostrou uma evolução dirigida para a estirpe B/ Sichuan/379/99 que viria a integrar a vacina antigripal em 2001/2002. Consequentemente, observou-se a co-circulação de duas linhagens diferentes evidenciada pela análise filogenética das estirpes B isoladas no nosso país.
- Comparative analysis of hybrid‑SNP microarray and nanopore sequencing for detection of large‑sized copy number variants in the human genomePublication . Silva, Catarina; Ferrão, José; Marques, Bárbara; Pedro, Sónia; Correia, Hildeberto; Valente, Ana; Rodrigues, António Sebastião; Vieira, LuísBackground: Nanopore sequencing is a technology that holds great promise for identifying all types of human genome variations, particularly structural variations. In this work, we used nanopore sequencing technology to sequence 2 human cell lines at low depth of coverage to call copy number variations (CNV), and compared the results variant by variant with chromosomal microarray (CMA) results. Results: We analysed sequencing data using CuteSV and Sniffles2 variant callers, compared breakpoints based on hybrid-SNP microarray, nanopore sequencing and Sanger sequencing, and analysed CNV coverage. From a total of 48 high confidence variants (truth set), variant calling detected 79% of the truth set variants, increasing to 86% for interstitial CNV. Simultaneous use of the 2 callers slightly increased variant calling. Both callers performed better when calling CNV losses than gains. Variant sizes from CMA and nanopore sequencing showed an excellent correlation, with breakpoints determined by nanopore sequencing differing by only 20 base pairs on average from Sanger sequencing. Nanopore sequencing also revealed that four variants concealed genomic inversions undetectable by CMA. In the 10 CNV not called in nanopore sequencing, 8 showed coverage evidence of genomic loss or gain, highlighting the need to improve SV calling algorithms performance. Conclusions: Nanopore sequencing offers advantages over CMA for structural variant detection, including the identification of multiple variant types and their breakpoints with increased precision. However, further improvements in variant calling algorithms are still needed for nanopore sequencing to become a highly robust and standardized approach for a comprehensive analysis of genomic structural variation.
- Deleção intersticial 7q33q34 em fetos de gravidez gemelar monocoriónica diamnióticaPublication . Simão, Laurentino; Marques, Bárbara; Ferreira, Cristina; Serafim, Sílvia; Alves, Cristina; Silva, Marisa; Viegas, Mónica; Peliano, Ricardo; Brito, Filomena; Bernardeco, Joana; Cruz, Jader; Pedro, Sónia; Martins, Ana; Tarelho, Ana; Carvalho, Inês; Cohen, Álvaro; Correia, HildebertoIntrodução: O acompanhamento de gestações gemelares pode revelar-se desafiante se houver alterações ecográficas e discrepâncias entre os fetos. Deleções intersticiais 7q, abrangendo diferentes regiões e apresentando tamanho variável, são raras, e encontram-se quase exclusivamente descritas em pós-natal. Objectivos: Apresentamos o caso de uma gestante, de 32 anos, com gravidez gemelar monocoriónica e diamniótica de 16 semanas, referenciada por bolsas jugulares bilaterais, crescimento no P10-P20 e discrepância no pico sistólico de velocidade da artéria cerebral média (PSV-ACM). Foi efetuada colheita de liquido amniótico para estudo por microarray cromossómico (CMA). Metodologia: Foi efeituado diagnóstico rápido de aneuploidias (DRA) por QF-PCR (Devyser®), ao que se seguiu CMA com array CytoScan 750K (Thermo Fischer®) e cariótipo. Resultados: O DRA revelou um resultado normal. O CMA permitiu a identificação de uma deleção intersticial com 9,0 Mb em 7q33q34 - arr[GRCh37] 7q33q34(133411316_142427027)x1. A alteração engloba 12 genes mórbidos. O cariotipo confirmou o resultado: 46,XX,del(7)(q32.3q34)dn. Após aconselhamento genético, o casal optou por interrupção da gestação. Conclusões: Deleções intersticiais na região 7q32 a 7q35 apresentam grande variabilidade fenotípica. As características mais comuns são: atraso de desenvolvimento e da linguagem, défice intelectual, dismorfias faciais e atraso de crescimento. Nos raros casos descritos com alterações cromossómicas parcialmente sobreponíveis ao caso em estudo, a CNV tem sido classificada como patogénica. No único caso com referência ao período pré-natal e com alteração quase totalmente sobreponível, descreve-se decréscimo de movimentos fetais, baixo peso à nascença, atraso de desenvolvimento, défice intelectual, dismorfias faciais e infeções múltiplas. A alteração cromossómica encontrada poderá explicar a relativa restrição de crescimento fetal, não tendo as bolsas jugulares, presentes em ambos os fetos e a discrepância PSV-ACM sido até agora descritos. Gestações com alterações ecográficas e CNVs, mas com reduzida bibliografia, são desafiantes na interpretação dos resultados a nível laboratorial e clínico. Só a descrição de mais casos permitirá um ganho de conhecimento em saúde.
- Detection of copy number variants in the human genome: Is long-read sequencing an alternative to genomic microarrays?Publication . Silva, Catarina; Ferrão, José; Marques, Barbara; Pedro, Sónia; Correia, Hildeberto; Rodrigues, António Sebastião; Vieira, LuísIntroduction: Copy number variations (CNVs) represent ~13% of the human genome and can harbour important genes and regulatory elements. High-resolution whole genome microarray (MA) analysis is the gold standard tool for detection of CNVs associated with genetic disorders. While short-read sequencing (SRS) can address SV detection, the use of long-read sequencing as proven to overcome SRS mapping inaccuracy in highly repetitive DNA regions and improve genome contiguity. We applied whole genome nanopore sequencing (NS) to call CNVs and compared the results with those obtained by microarray. Methodology: Genomic DNA from 2 cell lines (EOL-1 and 697) were processed using the CytoSan HD Array (Affymetrix) and ChAS software (ThermoFisher). A minimum CNV calling size threshold of 35 Kb was used. DNA was also sequenced on the MinION device (Oxford Nanopore Technologies) following a rapid library preparation method. Sequencing data were basecalled using Guppy, mapped with LRA, and SVs called using both CuteSV and Sniffles2. Sanger sequencing was performed to demonstrate breakpoint positions for 3 CNVs. R packages were used to perform comparisons between MA and NS data. Results: A total of 49 CNVs were confirmed after curated MA analysis in both cell lines, ranging in size from 35 Kb to 79 Mb. From those, 43 CNVs (87.7%) were called in nanopore data by either one (4 CNVs) or both (39 CNVs) callers with a mean whole genome coverage of ~12X. Six of 43 CNVs were called as inversions instead. In 3 CNVs the size of the variant was found to be smaller (ranging from ~5 to 22 Kb) than the threshold of MA analysis. The correlation between CNV sizes obtained with MA and NS was of 0.71 with Sniffles2 and 0.74 with CuteSV, whereas the correlation between callers was of 0.99. The breakpoint precision obtained for NS was much higher (ranging for CuteSV from 2 to 42 bp; and for Sniffles2 from 0 to 87 bp) than the one obtained for MA (ranging from 774 to 7618 bp). Conclusions: NS technology proved to be technically effective in the detection of CNVs of different types and sizes and thus posing itself as an alternative to MA in the detection of pathogenic SVs associated with genetic diseases. However, NS data analysis requires fine-tuning of the analysis conditions as well as the use of different methods, for greater reliability of results in a clinical context.
- Grupo de Trabalho sobre Ocorrência Microbiológica na Cadeia Alimentar (GTOMCA): trabalho desenvolvido e perspetivas futurasPublication . Viegas, Silvia; Brazão, Roberto; Pedro, Sónia; Ribeiro, VerónicaPonto de situação em 2016 sobre o trabalho desenvolvido e perspetivas futuras do Grupo de Trabalho sobre Ocorrência Microbiológica na Cadeia Alimentar (GTOMCA), apresentado no âmbito da reunião anual do PortFIR - Portal de Informação Alimentar (http://portfir.insa.pt/). O PortFIR é um programa de implementação de redes de excelência Portuguesas em nutrição e segurança alimentar e um portal que inclui bases de dados sustentáveis e de qualidade reconhecida sobre Composição e Contaminação de Alimentos e Consumos Alimentares.
- Grupo de trabalho sobre Ocorrência Microbiológica na Cadeia Alimentar (GTOMCA): trabalho desenvolvido e perspetivas futurasPublication . Viegas, Silvia; Brazão, Roberto; Pedro, Sónia; Ribeiro, VerónicaApresentação dos resultados do trabalho desenvolvido em 2015 e perspetivas futuras do grupo de trabalho sobre Ocorrência Microbiológica na Cadeia Alimentar (GTOMCA)
- Incidental X Linked Findings A female fetus with a gain in the DMD genePublication . Marques, Bárbara; Serafim, Silvia; Pedro, Sónia; Ferreira, Cristina; Simão, Laurentino; Alves, Cristina; Viegas, Mónica; Silva, Marisa; Brito, Filomena; Amorim, Marta; Correia, Joaquim; Correia, HildebertoIn prenatal diagnosis, chromosomal microarray analysis (CMA) has not yet fully replaced conventional cytogenetic but has rapidly become the recommended genetic test in pregnancies with ultrasound abnormalities. This methodology allows the identification of pathogenic small copy number variation (CNVs) in 5-10% of pregnancies with ultrasound abnormalities and a normal karyotype, increasing the diagnostic yield. However, this increased resolution can also result in the detection of incidental findings. Here we report a fetus referred for prenatal diagnosis due to skeletal dysplasia. Affymetrix Cytoscan HD chromosome microarray analysis was performed and a 204 kb gain was detected at Xp21.1 region (chrX: 31993622_32191110 [GRCh37]) in a female fetus, encompassing the intron 44 of the DMD gene, for the largest gene transcript. Nevertheless, if we considered the smaller transcripts it encompasses exon 1. The gain was maternally inherited. The DMD gene is involved on Becker muscular dystrophy, Cardiomyopathy, dilated, 3B and Duchenne muscular dystrophy. Intron 44 is a preferential breakpoint in about 30% of all DMD deletions, being the DMD transcript NM_004006.2 responsible for dystrophin expression in the skeletal muscle.The FGFR3 gene sequencing revealed the presence of the c.1118A >G, p.Y373C mutation associated to Thanatophoric Dysplasia, type 1 (TD1) justifying the ultrasound abnormalities.With this case, we reinforce that the discovery of CNVs in prenatal CMA goes beyond the correlation with the CNV and the ultrasound abnormalities. Incidental findings can also have a larger impact to the family clinical managing, even if not for the ongoing pregnancy for the reproductive future of the couple.
- «
- 1 (current)
- 2
- 3
- »