RESUMO
OBJECTIVES: Chromosomal mosaicism in chorionic villi (CV) is detected in ~1-2% of cases. When a mosaic in CV is detected during prenatal diagnosis, a confirmatory karyotype should be performed on amniocytes to discriminate between a mosaic confined to the placenta [confined placental mosaicism (CPM)] and one generalized to the fetus [true fetal mosaicism (TFM)]. We determined the likelihood that any mosaic abnormalities identified through CV samples are confirmed in the fetus. METHODS: Over a period of 14 years, the laboratory analyzed both the cytotrophoblast and the mesenchyme of 60 347 CV samples. Cytogenetic results from CV samples showing mosaicism with follow-up amniocentesis were considered. The incidence of CPM and TFM and the risk of confirmation in the amniotic fluid (AF) were calculated. Uniparental disomy (UPD) was tested on ~300 cases at risk due to involvement of an imprinted chromosome. RESULTS: Overall, 1317 mosaic CV cases (2.18%) were detected, of which 1001 were subsequently investigated by amniocentesis. The overall risk of TFM was 13% and UPD incidence was 2.1%. CONCLUSIONS: The very large presented sample set and consistency in cytogenetic methodology, especially the analysis of both placental layers performed on all CV samples will enable genetic counselors to determine the risk of fetal involvement and the clinical relevance of an identified mosaic condition.
Assuntos
Vilosidades Coriônicas/metabolismo , Feto/metabolismo , Mesoderma/metabolismo , Mosaicismo , Trissomia/diagnóstico , Trofoblastos/metabolismo , Dissomia Uniparental/genética , Amniocentese , Líquido Amniótico , Amostra da Vilosidade Coriônica , Feminino , Humanos , Cariotipagem , Placenta/metabolismo , Gravidez , Diagnóstico Pré-Natal , Estudos RetrospectivosAssuntos
Análise Citogenética/métodos , DNA/sangue , Feto/metabolismo , Trissomia/diagnóstico , Síndrome de Turner/diagnóstico , Amniocentese , Âmnio/citologia , Amostra da Vilosidade Coriônica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Mosaicismo , Gravidez , Diagnóstico Pré-Natal , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Síndrome de Turner/genéticaRESUMO
OBJECTIVES: Karyotyping on chorionic villous samples (CVS) includes the analysis of both cytotrophoblast (STC) and mesenchyme (LTC). This approach requires complex laboratory organization and trained technicians. The introduction of quantitative fluorescent polymerase chain reaction (QF-PCR) instead of conventional karyotyping in low-risk pregnancies opened its application in CVS analysis. Discordant QF-PCR and CVS cytogenetic results were reported, and strategies for CVS analysis were introduced to minimize this risk. The possibility to substitute the STC with QF-PCR was reported. The aim of this study is to evaluate benefits and limitations of the approach QF-PCR + LTC compared with the traditional method STC + LTC and to quantify the associated risks of false results. METHOD: This study is based on a retrospective cytogenetic audit of CVS results (n = 44 727) generated by the STC + LTC analytic approach. False-negative risks related to true fetal mosaicism type IV, imprinting syndromes and maternal contamination in LTC were calculated. RESULTS: Compared with STC + LTC, QF-PCR + LTC approach is associated with a cumulative false-negative risk of ~1/3100-1/4400. Costs and reporting time of STC in a high-throughput cytogenetic lab are similar to a CE-IVD marked QF-PCR analysis. CONCLUSIONS: These results should be clearly highlighted in the pre-test counseling and extensively discussed with the couple prior to testing for informed consent.