Browsing by Author "Pires, Sílvia"
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- Défice Cognitivo e Alterações de Comportamento: Investigação Etiológica sob um Olhar RenovadoPublication . Serra Nunes, Isabel; Monteiro, Joana; Oliva Teles, Natália; Pires, Sílvia; Gomes, Lúcia; Monteiro, Virgínia
- Detection of subtelomeric rearrangements in 1180 patients: FISH and MLPA contributionPublication . Mota Freitas, Manuela; Ribeiro, Joana; Candeias, Cristina; Lopes, Elisa; Oliveira, Fernanda Paula; Aguiar, Joaquim; Ribeiro, Maria Céu; Pires, Sílvia; Oliva Teles, Natália; Correia, Hildeberto; Fonseca Silva, Maria LuzMental retardation (MR) is a major social, educational, and health problem affecting 3% of the population. Subtelomeric chromosome aberrations are one of the major causes of MR with or without multiple anomalies; previous studies have shown that these rearrangements are responsible for 3-6% of unexplained mental retardation. Between 2000-2010 in the Cytogenetics Unit, Centro de Genética Médica Jacinto de Magalhães, INSA (Portugal), the subtelomeric regions of all the chromosomes were analysed in 1180 individuals, whose karyotype had been considered normal. The reasons for referral included (i) psychomotor development delay or (ii) mental retardation with or without dysmorphisms. Until 2007 the analysis of metaphases, obtained from cultured lymphocytes following standard protocols, were performed by "Fluorescence in situ hybridization” (FISH): the first kit to be used was the Chromoprobe Multiprobe-TM (Cytocell) kit (until 2005), which was followed by the TotelVysion Multi-Color FISH Probe (Vysis). In 2007 the "Multiplex Ligation dependent Probe Amplification” (MLPA) was implemented in the laboratory, using kits P036 and P070 (MRC-Holland). All the unbalanced cases detected by MLPA were confirmed by FISH. Of a total of 1180 individuals, 62 (5.3%) showed chromosomal alterations: 60 in the subtelomeric regions and 2 in the control regions. It was not possible to perform any familial studies in 12 of the 62 cases (1.0%) and therefore the results were considered inconclusive. In the other 50 abnormal cases, the parental investigation allowed us to conclude that 30 (2.5%) of these patients had chromosomal abnormalities “de novo” that might be responsible for the clinical phenotype; the remaining 20 possibly abnormal cases (1.7%) were considered polymorphisms without pathological significance, since the apparent deletion or duplication had been inherited from phenotypically normal parents. The authors compare the results obtained in the individuals in the present study with literature reports and highlight the advantages/disadvantages of each technique.
- Prenatal diagnosis of a partial dup (16p) due to a rare recombinant resulting from a paternal intrachromosomal insertionPublication . Pires, Sílvia; Fonseca Silva, Maria da Luz; Rosa Pereira, Ana; Meireles, Alexandra; Oliva Teles, Natália; Ribeiro, Joana; Mota Freitas, Manuela; Marques, Bárbara; Soares, Gabriela; Brandão, Otilia; Correia, HildebertoChromosomal rearrangements involving three break-points are relatively rare, about 1/5,000 live births. When a chromosomal segment is moved from one part of a chromosome into another part of the same chromosome, it is considered an intrachromosomal insertion; the orientation of the inserted material in relation to the centromere may remain the same, resulting in a direct insertion, or reversed, resulting in an inverted insertion. A single crossover in the gametogenesis between any of the three breakpoints may result in unbalanced recombinants, leading to phenotypic consequences in the offspring. Partial trisomy 16p is a rare chromosomal imbalance characterized by mental retardation, prenatal and post-natal growth deficiency, facial anomalies, cleft palate, congenital heart defects, and urogenital anomalies. Previous studies have established that the phenotype of this condition is not related to the extension of the duplicated segment and that the region 16p13.1–p13.3 is critical in determining this disorder. We report on a prenatal diagnosis performed at 14 weeks. The fetus presented with an increased fetal nuchal translucency and thus was referred for con- ventional cytogenetic studies. The chromosomal analysis of the amniotic fluid cells revealed a structurally abnormal chromosome 16, with additional material on 16q. The maternal karyotype was normal, but the father carried an intrachromosomal insertion in chromosome 16: a between-arm insertion of a small segment of the short arm into the distal region of the long arm. To characterize the extension of the imbalance in the fetus, chromosome comparative genomic hybridization (cCGH) analysis was performed. Fetus karyotype: 46,XY,rec(16)dup(16p)ins(16) (q24p13.2p13.3)pat.ish cgh dup(16)(p13.2p13.3). The authors emphasize the rarity of this case, explain its possible formation mechanism and compare the fetal phenotype (available after autopsy) with similar cases described in the literature
- Statistical Approach to Prenatal Zygosity Assessment Following a Decade of Molecular Aneuploidy ScreeningPublication . Pires, Sílvia; Nogueira, António J.A.; Pinho, Odília; Delgado, Tiago; Sousa, Mário; Santos, Rosário; Jorge, PaulaIn twin pregnancy studies, molecular genetic techniques have rarely been used to determine zygosity, despite their known precision and accuracy. The present work aimed to assess the power of discrimination in zygosity assessment, using a set of microsatellite markers that were routinely used for aneuploidy screening by multiplex-PCR in a prenatal context. Rapid aneuploidy screening using a group of 20 microsatellite markers (STRs) located on chromosomes 13, 18, 21 and X has been performed in our lab for over 10 years, with a total of approximately 1,500 samples studied to date. A retrospective analysis of the 257 prenatal samples from multiple pregnancies was carried out. A subset of 14 cases presenting theoretical monozygosity were re-evaluated by the use of biostatistics tools accessed via the ZygProb website. Further monozygosity determination relative to dizygosity was calculated, given an estimated overall error value of 0.093%. The results show that monozygosity had been correctly determined in all our previously studied twins. This work demonstrates that accurate zygosity assessment can be achieved with the same STRs applied in aneuploidy screening with a high power of discrimination and a matching probability of over 99.999999%.