RESUMO
BACKGROUND: PWS is challenging to diagnose prenatally due to a lack of precise and well-characterized fetal phenotypes and noninvasive markers. Here we present the case of prenatal diagnosis of Prader-Willi syndrome, which was suspected with whole-genome NIPS. METHODS: Whole-genome noninvasive prenatal screening showed a high risk for trisomy 15. Amniocentesis followed by FISH analysis and SNP-based chromosomal microarray was performed. RESULTS: Simultaneous analysis of maternal and fetal samples with SNP microarrays demonstrated maternal uniparental disomy (UPD). CONCLUSION: The presented case is the first case of PWS described in detail, which was suspected by NIPS results. It demonstrates that the choice of confirmation methods concerning the time needed is crucial for the right diagnosis. We suppose that prenatal testing of UPD is essential for chromosome regions, which play a key role in the appearance of various gene-imprinting failure syndromes like PWS or AS.
Assuntos
Teste Pré-Natal não Invasivo/métodos , Síndrome de Prader-Willi/genética , Dissomia Uniparental/genética , Adulto , Amniocentese/métodos , Cromossomos Humanos Par 15/genética , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Síndrome de Prader-Willi/diagnóstico , Gravidez , Dissomia Uniparental/patologiaRESUMO
OBJECTIVES: The aim of this study was to establish maternal contribution to false positive noninvasive prenatal DNA screening (NIPS) results and develop the method to distinguish maternal and fetal origin of high-risk monosomy X NIPS calls including mosaic maternal cases. METHOD: A total of 906 women carrying singleton pregnancies have been recruited. Maternal plasma DNA semiconductor massive parallel sequencing was performed to detect common aneuploidies. For the case of high monosomy X risk call, analysis method to distinguish fetal and maternal monosomy X has been additionally applied. RESULTS: According to NIPS results, 18 patients had a high risk of fetal monosomy X. In 11 (61%) cases, fetal aneuploidy was confirmed by karyotyping. Other 7 cases were false positives. In 3 out of 7 cases, additional analysis based on in silico size selection was allowed to assume maternal monosomy X. In these cases, fluorescence in situ hybridization analysis confirmed mosaic monosomy X in maternal blood cells. CONCLUSION: The prevalence of mosaic monosomy X karyotype is 0.3% (3/906)-10 times higher than published before. Additional in silico size-selection and data analysis increases PPV for monosomy X from 61% to 73% for studied population.