Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more ...often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.
Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this ...technology.
The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar21/46,XX19) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.
Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.
The study was aimed to determine diagnostic application of MLPA for rapid prenatal identification of chromosome 13, 18, 21 and X and Y aneuploidies.
409 amniotic fluid samples from amniocentesis for ...fetal karyotyping were studied. DNA was isolated using the QIAmp DNA Blood Midi Kit (348 samples) or through proteinase K treatment (61 samples). SALSA MLPA P095 probes (mrc-Holland) were used to detect aneuploidy
In 324 studies (79.2%) diagnostic results were obtained. Chromosomal aberrations were found in 16 cases (4.9%). These results were concordant with standard karyotype. In 3 cases (0.92%) false negative results were found but all abnormalities were undetectable with MLPA.
MLPA is a reliable method of rapid prenatal detection of aneuploidy
The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal ...aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.
A large number of cases with supernumerary marker chromosomes (SMCs) should be compared to achieve a better delineation of karyotype-phenotype correlations. Here we present four phenotypically ...abnormal patients with autosomal marker chromosomes analysed by fluorescence in situ hybridisation using centromeric, telomeric, and unique sequence probes, as well as forward and reverse painting. We also report the first case, to the best of our knowledge, of an SMC derived from chromosome 5. Furthermore, a marker chromosome 20 in a patient with sex differentiation abnormalities, a double mar(6) in a boy with psychomotor retardation, and the association of r(19) with dup(21q21.2q22.12) are described. Although the mar(6) was very small, the presence of euchromatin was shown, suggesting that the partial trisomy of pericentric region derived sequences is implicated in the aetiology of the abnormal phenotypes.
Triploidy, the presence of an additional haploid set of chromosomes, is the cause of 20% of spontaneous abortions, premature births and perinatal deaths. The most common clinical signs of triploidy ...are: severe intrauterine growth retardation, macrocephaly, total syndactyly of third and fourth fingers and CNS, heart and renal defects. Hydatidiform mole, one of the characteristic features of pure triploidy, is found in more than 90% of cases. The survival of individuals with diploid/triploid mixoploidy is usually longer than of those with pure triploidy. The detailed clinical characteristics of two of our patients with triploidy diagnosed shortly after birth are presented. In one of them mixoploidy (lymphocytes/fibroblasts) was confirmed. In the second pure triploidy was identified in cultured lymphocytes. We discuss the clinical features in our patients and compare them with data from medical literature.
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