Browsing by Author "Mourinha, V."
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- 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.
- 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).