Browsing by Author "Silva, M."
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- Chromosomal disorders and male infertilityPublication . Simão, L.; Caetano, I.; Pedro, S.; Silva, M.; Ambrósio, P.; Gonçalves, J.; Brito, F.; Marques, B.; Alves, C.; Serafim, S.; Geraldes, M.C.; Correia, H.Male factor infertility is considered a complex disorder with a largely unknown etiology that affects about 7% of men. In general, genetic abnormalities account for 15%-30% of condition and Y chromosome microdeletions are also frequent. The study, based on our casuistic, aimed at contributing to a better understanding of the genetic causes of infertility. A group of 410 idiopathic infertile men with non-obstructive azoospermia, oligozoospermia, or unknown semen quality (based on clinical evaluation and/or sperm counts) was retrospectively selected. Conventional karyotype was performed in all samples; Y microdeletion screen was performed in 247 samples. Forty two abnormal karyotypes (10.2%) were found, indicating an elevated frequency of chromosome abnormalities among the selected infertile men, as compared to that of newborn populations (≈0.4%). This frequency is higher than that reported in most similar studies that pointed to frequencies ranging from 2.2%-14.3%. Klinefelter´s syndrome was the most common chromosome disorder (4.9%). There were 18 cases with 47,XXY karyotype and 2 cases of mosaicism involving lines 47,XXY and 46,XY. Reciprocal translocations were identified in 10 cases (2.4%), particularly in men with unknown semen quality. Overall, reciprocal translocations have been found in approximately 1% of the infertile men and more commonly in azoospermics than in oligozoospermics. However, this type of association was not found in the present study. On the other hand, Y microdeletions were identified in 16/247 cases (6.5%), more frequently in azoospermics (13.3%, corresponding to 8/60 azoospermics). Among these 8 cases, 7 presented deletions at the AZFc region. The marked presence of chromosomal abnormalities and Y microdeletions enphasizes the relevance of studying both factors in infertile men to improve genetic counseling, to allow the development of appropriate therapies, and to expand the knowledge about the ethiology of male infertility.
- Diagnóstico pré-natal tardio de uma gestação com anomalias ecográficas e com duplicação da região 7q11.23Publication . Simão, L.; Serafim, S.; Ferreira, C.; Alves, C.; Brito, F.; Silva, M.; Furtado, J.; Viegas, M.; Pedro, S.; Marques, B.; Rodrigues, M.; Sá, J.; Castro, M.J.; Mendes, P.; Vassal, H.; Correia, H.Introdução: O diagnóstico pré-natal (DPN) atempado de anomalias cromossómicas em fetos com anomalias ecográficas é fundamental no prognóstico da gravidez, ou na sua possível interrupção. Assim, a realização das ecografias fetais nas semanas preconizadas é determinante para a gestão dos casos anormais. Descrevemos um caso de uma gravidez mal vigiada, com ecografia fetal realizada às 29 semanas de gestação, onde se identificou uma dilatação pielo-calicial grave no rim esquerdo e dúvida na área cardíaca. Objectivos: Evidenciar que a vigilância atempada das gestações conjuntamente com a análise por microarray aumenta a capacidade de diagnóstico em gestações com anomalias fetais detetadas ecograficamente.
- DNA damage and oxidative DNA damage in Inflammatory Bowel DiseasePublication . Pereira, C.; Coelho, R.; Grácio, G.; Dias, C.; Silva, M.; Peixoto, A.; Lopes, P.; Costa, C.; Teixeira, J.P.; Macedo, G.; Magro, F.
- Mudanças no diagnóstico pré-natal cromossómico: indicações clínicas, amostras biológicas, metodologias e cromossomopatiasPublication . Simão, L.; Silva, M.; Alves, C.; Brito, F.; Serafim, S.; Ambrósio, P.; Geraldes, M.C.; Marques, B.; Ferreira, C.; Pedro, S.; Furtado, J.; Ventura, C.; Tristão, J.; Ferreira, A.; Correia, J.; Correia, H.Introdução: As mudanças no diagnóstico pré-natal de anomalias cromossómicas (DPN) nos últimos 10-15 anos foram contínuas e significativas. Objetivos: Propômo-nos analisar essa evolução: mudanças nas indicações clínicas; introdução das biópsias de vilosidades coriónicas (BVC); utilização do diagnóstico rápido de aneuploidias (DRA); estudos por microarray; alterações cromossómicas encontradas. Metodologia: Fez-se a avaliação retrospetiva nas gestações com amostras estudadas nos triénios 2004-2006 e 2014-2016. Analisaram-se os parâmetros indicação clínica, tipo de amostra, metodologias utilizadas e resultados. Resultados: Identificaram-se 68 fetos com cariotipo anormal em 2210 cariotipos (3,1%) em 2004-2006 e 208 fetos com cariotipo anormal em 2315 cariotipos (9,0%) em 2014-2016. A maior frequência de anomalias encontrou-se nos casos de rastreios ecográficos e combinados indicativos de risco acrescido de anomalia numérica e de progenitores portadores de alterações cromossómicas. As BVC permitiram respostas precoces nas gestações com anomalias numéricas e, adicionalmente, um aumento desses cariotipos (7.5% das amostras). O DRA permitiu ter uma resposta rápida nas anomalias numéricas mais frequentes (2 dias). As anomalias estruturais foram menos preponderantes nos cariotipos anormais (32,4% em 2004-2006 e 14.4% em 2014-2016). Discussão e conclusões: O DRA reduziu o tempo de resposta e das decisões sobre o futuro das gestações. O microarray permitiu identificar alterações sindromáticas em situações não resolúveis por outras metodologias. A utilização de BVC permite estabelecer uma melhor correlação fenotipo-genotipo em menores idades gestacionais. No entanto, as gestações com anomalias numéricas têm algum risco de perda fetal no primeiro e início do segundo trimestres. Assim, algumas BVC com cariotipos anormais resultariam em perdas espontâneas, o que poderia disponibilizar outros casos para DPN. Por outro lado, o menor número de anomalias estruturais equilibradas encontrado pode reduzir o conhecimento da variação genética nas famílias e na população. Um novo paradigma resulta da implementação dos testes não invasivos no DPN, para os quais ainda não conhecemos todas as limitações e repercussões.
- Multiple non contiguous copy gains and a terminal loss in 8q24 identified in a fetus with cleft palate and lipPublication . Serafim, S.; Pedro, S.; Marques, B.; Tarelho, A.R.; Ferreira, C.; Simao, L.; Viegas, M.; Silva, M.; Alves, C.; Mourinha, V.; Ferreira, A.; Correia, H.Objectives: Chromosomal microarray analysis (CMA) is the recommended genetic test in pregnancies with ultrasound abnormalities but in some cases karyotype may still be needed to clarify the underlying mechanism of complex rearrangements. Here we report the case of a fetus from a healthy 24-year-old G1P0 woman, with a low risk for common aneuploidies in the 1st trimester prenatal screening but referred for CMA at 17+6 weeks of gestation due to cleft palate and lip in the 1st trimester ultrasound. Method: After a normal result in the rapid aneuploidy diagnostic test we performed CMA using ThermoFisher Cytoscan™ 750K. Our reporting resolution includes gains and losses larger than 35 Kb, considered clinically relevant for the course of the pregnancy. In this case further tests were done to assess recurrence risk and a possible chromosomal rearrangement: CMA and karyotype on the parents and karyotype on the fetus. Results: The CMA profile revealed a female fetus with three non-contiguous interstitial copy gains and a terminal loss in the long arm of chromosome 8 (8q24), as follows: - x4 copy gain at 8q24.12q24.13 with 585 Kb - x2 copy neutral region with 1.5 Mb - x4 copy gain at 8q24.13 with 2.9 Mb - x2 copy neutral region with 1.2 Mb - x3 copy gain at 8q24.21q24.23 with 17.8 Mb - x1 terminal loss at 8q24.3 with 130 Kb The fetal karyotype showed, in one of the chromosomes 8, an abnormal pattern in the long arm with a larger relative size. After parental studies the reported copy number variants were shown to be de novo. Conclusions. Most of the cases reported in the literature with gains along 8q result from a rearrangement involving another chromosome making it challenging to assess a genotype-phenotype correlation (PMID: 34265769; PMID: 31141803; PMID: 34794751). The few cases of individuals reported with isolated gains in the 8q24 have been described as having different features, depending on the size of the gain, and those may include facial dysmorphysms, clef lip and palate, developmental delay, among others (PMID: 25506438; PMID: 11484205; PMID: 33316910; UNIQUE - rarechromo.org: duplications of 8q). Recently a fetus with multiple congenital abnormalities, including clef palate, was reported having a similar imbalance, and although the parents decided to keep the pregnancy the baby died soon after birth given the extension of the congenital abnormalities (PMID: 30638476). The CMA results in our case explained the clef palate and lip identified in the fetus and, after genetic counseling, the parents opted to terminate the pregnancy. Although the identified non-contiguous gains and the terminal loss may suggest a mechanism of chromothripsis/chromoanagenesis for the arising of this abnormal chromosome 8, no further studies were performed after determining that the parents had a normal result and therefore a low recurrence risk for future pregnancies.
- Predictive power of HLA-DQB1 to identify narcoleptic patientsPublication . Silva, M.; Lopes, J.; Carvalho, C.; Cunha, D.; Costa, P.P.; Martins da Silva, A.Introduction The determination of HLA class II genotype is widely used to confirm the diagnosis of Narcolepsy without (N) or with Cataplexy (NC). The use of HLA genotyping in clinical diagnosis is reliable and is a contributing factor to the reinforcement of the wide acceptance of the hypothesis of autoimmune origin for Narcolepsy. We evaluate the contribution of genetic markers (HLA) in the differential diagnosis between narcolepsy with and without Cataplexy and their relevance in the context of our population (Northern Portugal). Materials and methods A cohort of 53 patients with Narcolepsy with Cataplexy (NC) or without (N) was studied. Patients followed up to the Outpatient Sleep Clinic of Hospital Santo António/CH Porto were assessed by clinical, night sleep polygraphic recording, MSLT on the following day. Blood sampling for HLA-DQB1∗ analysis was performed after informed consent. The genotyping was achieved by using a PCR-Sequence Specific Primer (SSP) methodology. Control Population (CP) comprised 206 reportedly healthy individuals from the same geographic origin. Data from laboratory parameters was confronted with the clinical diagnostic hypothesis. Patients’ clinical reevaluation was considered if phenotype-genotype did not match. Results Of the 53 patients, 14 were classified as N and 39 as NC. The frequency of HLA-DQB1∗06:02 allele was overrepresented in N and NC patients (43% and 69%, respectively) when compared with the control population (16%) – p value = 1.38 × 10–12 for NC. Interestingly the frequency of the HLA- DQB1∗03 allele was decreased in NC patients (36% NC vs. 56% CP, p = 0.01917). No differences were found in other DQB1∗06 frequencies between the cohort of patients and the control population. Conclusion The HLA-DQB1∗06:02 allele, a susceptibility factor for other autoimmune disorders, was confirmed as the most important susceptibility allele to NC in our population. The frequency of this allele in our NC patients (69%) is within the range of other studies. Such values pointed out to 11.8 OR for NC comparing with 3.9 OR for N patients. These findings point out to the relevance of the allele DQB1∗0602 in this sleep entity and on the autoimmune involvement in the picture of Narcolepsy–Cataplexy.
- Prenatal diagnosis of 7q11.23 duplication in a fetus with renal pelvic dilatation and the postnatal outcomePublication . Serafim, S.; Ferreira, C.; Simão, L.; Alves, C.; Brito, F.; Silva, M.; Furtado, J.; Viegas, M.; Pedro, S.; Marques, B.; Rodrigues, M.; Sá, J.; Castro, M.J.; Mendes, P.; Vassal, H.; Correia, H.7q11.23 duplication syndrome is a multisystemic developmental disorder characterized by variable manifestations, such as speech delay, mild craniofacial anomalies with distinctive facial features, and intellectual ability ranging from mental retardation to normal cognitive development. Approximately 30% of individuals with 7q11.23 duplication have one or more congenital anomalies. Penetrance is complete with variable expression of phenotypic features. Prevalence has been estimated at 1:7,500-1:20,000. The 7q11.23 duplication is frequently inherited from a parent. Here we report a 33-year-old woman referred for prenatal diagnosis at 29 weeks of gestation due to fetal renal pelvic dilatation. Chromosomal microarray analysis (CMA) was performed after a normal molecular rapid aneuploidy test result and identified a 1.44 Mb duplication at 7q11.23 - arr [GRCh37] 7q11.23 (72,700,467-74,136,633)x3 - overlapping the 7q11.23 duplication syndrome region, in a female fetus. The gain was inherited from the mother which had no previous clinical evaluation but a later reassessment revealed mild cognitive delay and language impairment. Delivery was at 35 weeks due to a maternal respiratory infection with acute pulmonary edema. Newborn resuscitation was required for neonatal respiratory depression with an Apgar score of 1'-2, 5'-4, 10 '-8. Birth weight and length was 2140g and 43cm respectively, with a head circumference of 32cm. In the neonatal period a transient systolic murmur was identified with no alterations on the echocardiogram. Renal and bladder ultrasound showed pelvic dilatation with no changes of the ureteral tract, suggesting a relation with ureteropelvic junction syndrome. Left pyeloplasty for the ureteropelvic junction syndrome was performed at 14 months of age. Clinical evaluation at the age of 22 months revealed psychomotor development delay with delayed speech, facial features overlapping Williams-Beuren syndrome, and the systolic murmur grade I/VI was still present. Growth and weight were both normal. To the best of our knowledge this is the second prenatal case of 7q11.23 duplication described. Although genitourinary tract abnormalities are not the most common feature in patients with 7q11.23 duplication, congenital anomalies of the urinary tract can occur in 15%-18%, including hydronephrosis and unilateral renal agenesis. This shows that the ultrasound abnormalities not always suggest a specific syndrome but after the identification of a pathogenic CNV made possible by the use of CMA a correlation may be achievable. Additionally the discovery of CNVs in prenatal CMA may go beyond the context of the current pregnancy allowing for the identification of carriers thus having a larger impact in a family's health management and genetic counseling.
- Prenatal diagnosis of idic(9)Publication . Simão, L.; Marques, B.; Cravo, J.; Ventura, C.; Correia, H.; Silva, M.; Mourinha, V.; Furtado, J.; Páramos, A.I.Tetrasomy of the short arm of chromosome 9 is a rare chromosome imbalance that may result from a supernumerary isochromosome 9 with the most recurrent breakpoints being 9p10, 9q12 and 9q13. On ultrasound, it usually presents with intrauterine growth restriction (IUGR), abnormal facial profile and ventriculomegaly. However, few reports establish a correlation between fetal features and the size of isochromosome or the presence of isodicentric 9. We report the clinical case of a 32-year-old pregnant woman, G2P1, underwent amniocentesis at 13 weeks of gestation with fetal increased nuchal translucency (7mm). The fetus also presented IUGR, cystic higroma, generalized subcutaneous edema, cardiac malformations, facial anomalies and fetal death. The karyotype was performed by standard in situ methods. Fluorescence in situ hybridization (FISH) was performed using centromeric probe CEP9. Conventional cytogenetic and FISH analyses revealed a supernumerary chromosome idic(9)(q12) in all cells examined. After counseling the couple opted for termination of pregnancy. The post-mortem analysis revealed a single umbilical arteria, IUGR, cystic higroma, facial dysmorphism with cleft lip and palate, hypertelorism and low set ears. These findings are in accordance with other reports. Nevertheless, the hypertelorism is not commonly described and such an early detection of a cardiac anomaly is uncommon. Additionaly the fetal death occurred early than in the most cases described in literature. Although breakpoint position effect on the severity on the phenotype is not consensual it has proposed that cases presenting with breakpoints on p10, on q12 or on q13 show a similar phenotype. However, cardiac defects seem more frequent on cases in which the abnormality includes 9q material. This work aims to contribute to a better karyotype-phenotype correlation in cases with tetrasomy 9p and isodicentric chromosomes idic(9).
- Risk assessment of exposure to multiple mycotoxins in foodPublication . Viegas, S.; Viegas, C.; Ramos, C.; Silva, M.; Sabino, R.; Verissimo, C.; Laura, R.Moulds may produce a diversity of toxins such as aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins and others. Although toxicological, environmental and epidemiological studies have addressed the problem of these toxins one by one, more than one mycotoxin are found usually in the same contaminated food. Risk assessment for humans potentially exposed to multimycotoxins suffers very much from the lack of adequate food consumption data. Furthermore, for a given mycotoxin, synergism and antagonism with other mycotoxins, found in the same food commodities, are not taken into account. Aflatoxin B1 and ochratoxin A belong to the most frequently occurring mycotoxins. This has repeatedly been demonstrated, however, normally, the risk resulting from their simultaneous occurrence is not considered. A descriptive study was developed to monitor air fungal contamination in one hospital food unit.
- Seasonal Dynamics and Spatial Distribution of Aedes albopictus (Diptera: Culicidae) in a Temperate Region in Europe, Southern PortugalPublication . Osório, H.; Rocha, J.; Roquette, R.; Guerreiro, N.; Zé-Zé, L.; Amaro, F.; Silva, M.; Alves, M.J.Aedes albopictus is an invasive mosquito that has colonized several European countries as well as Portugal, where it was detected for the first time in 2017. To increase the knowledge of Ae. albopictus population dynamics, a survey was carried out in the municipality of Loulé, Algarve, a Southern temperate region of Portugal, throughout 2019, with Biogents Sentinel traps (BGS traps) and ovitraps. More than 19,000 eggs and 400 adults were identified from May 9 (week 19) and December 16 (week 50). A positive correlation between the number of females captured in the BGS traps and the number of eggs collected in ovitraps was found. The start of activity of A. albopictus in May corresponded to an average minimum temperature above 13.0 °C and an average maximum temperature of 26.2 °C. The abundance peak of this A. albopictus population was identified from September to November. The positive effect of temperature on the seasonal activity of the adult population observed highlight the importance of climate change in affecting the occurrence, abundance, and distribution patterns of this species. The continuously monitoring activities currently ongoing point to an established population of A. albopictus in Loulé, Algarve, in a dispersion process to other regions of Portugal and raises concern for future outbreaks of mosquito-borne diseases associated with this invasive mosquito species.