RESUMEN
OBJECTIVE: Array technology in chorionic villus sampling (CVS) - analysis of clinical benefit and a proposal of a more effective 1st trimester genetic testing policy. DESIGN: Retrospective study. SETTING: Gennet, Center of Medical Genetics and Reproductive Medicine, Prague. MATERIAL AND METHODS: Total of 913 CVS were performed at Gennet between 2010-2014. All 913 samples were tested by QF-PCR rapid test for aneuploidy of chromosomes 13, 18, 21, X and Y and karyotyping following standard long term culture. Microarray analysis (Illumina HumanCytoSNP12 v2.1) was performed on 179 samples with normal result from both - QF-PCR and karyotyping. RESULTS: At 229 samples the common chromosomal aneuploidy was detected using rapid QF-PCR (25% from 911 successful rapid tests). Conventional karyotyping revealed 239 unbalanced chromosome aberrations (27% from 897 successful cultivations). 227/239 (95%) positive karyotypes confirmed QF-PCR finding of common aneuploidies. 10 unbalanced chromosome aberrations were not covered by rapid QF-PCR test. Microarray analysis of samples with normal result from both- QF-PCR and karyotyping- revealed 13 clinically relevant chromosome aberrations (7.5%). CONCLUSION: New policy for chorionic villi testing at Gennet was established. Based on evaluation of the results of karyotyping, array and QF-PCR and analysis of published data we decided to replace karyotyping by microarray analysis in all cases of foetuses with normal results from QF-PCR. More effective detection of pathological and clinically relevant chromosome aberrations in examined foetuses is expected.
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Trastornos de los Cromosomas/diagnóstico , Cariotipificación/métodos , Diagnóstico Prenatal/métodos , Aneuploidia , Muestra de la Vellosidad Coriónica , Femenino , Humanos , Reacción en Cadena de la Polimerasa/métodos , Valor Predictivo de las Pruebas , Embarazo , Primer Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVES: SNP array (array method using Single Nucleotide Polymorphisms) enables to detect cytogenetically undetectable submicroscopic alterations (microdeletions, microduplications), which could be also causative for ultrasonographic anomalies of fetus. This article describes the principle, advantages, disadvantages and application possibilities of the SNP array method in prenatal diagnosis. The ten month experience with SNP array use in prenatal diagnosis is presented. DESIGN: Prospective study. SETTINGS: Gennet, Prague. MATERIAL AND METHODS: During the period from April 2010 to January 2011 we performed 110 SNP array analyses of fetal DNA: 14 chorionic villi samples (CVS), 88 amniotic fluid samples (AMC), 1 cord blood sample and 7 miscarriage samples. Laboratory tests were carried out on DNA from both cultured and uncultured fetal cells. Examinations were performed in fetuses with sonographic abnormal findings having normal karyotype. In addition 14 fetal cytogenetic abnormalities were solved. SNP array analysis was performed using Illumina InfiniumHD HumanCytoSNP-12 chip. All data were analysed by Illumina KaryoStudio and GenomeStudio software. RESULTS: SNP array analysis was performed in 108 fetuses (only 2 examination failures, 1.8%). In total, we detected CNV (copy number variation) in 29 samples (29/108 = 27%). 15% (16/108) of fetuses with abnormal ultrasound findings were found to carry clinically relevant CNV. Probably benign CNVs were found in 8 samples (8/108 = 7%) and in additional 5 CNVs parental samples have not been analysed yet. Excluding karyotypically abnormal cases clinically relevant CNVs were found in 10% of fetuses (9/94). In all cases with de novo chromosomal aberration the clinical relevancy was clarified (imbalances in 50%). CONCLUSION: Our data suggest that SNP array analysis is a relevant and useful technique in prenatal diagnosis.
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Anomalías Congénitas/diagnóstico , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Diagnóstico Prenatal , Anomalías Congénitas/diagnóstico por imagen , Anomalías Congénitas/genética , Femenino , Humanos , Embarazo , Ultrasonografía PrenatalRESUMEN
Between January 1992 and March 1994 in Klimentska Screening Centre 635 second trimester amniocenteses were performed because of the risk of a chromosomal aberration. 416 (66 per cent) procedures were recommended because of the mother's age over 35 years and 219 ones (34 per cent) because of a positive screening test. Maternal serum alpha-fetoprotein and human chorionic gonadotrophin were used as screening markers in most cases. Five trisomy 21 cases in the advanced age group were detected. Serum markers were assessed in three older mothers with an affected foetus after amniocentesis. All were ex post screen positive. Three trisomy 21 foetuses of mothers younger than 35 years were detected in the screen positive group. Recent advances in screening for Down's syndrome and other congenital defects are discussed.