RESUMEN
OBJECTIVE: We previously reported on the validation of Prenatal BACs-on-Beads™ on retrospectively selected and prospective prenatal samples. This bead-based multiplex assay detects chromosome 13, 18, 21 and X/Y aneuploidies and the nine most frequent microdeletion syndromes. We demonstrated that Prenatal BACs-on-Beads(TM) is a new-generation, prenatal screening tool. Here, we describe the experience of five European prenatal diagnosis laboratories concerning the ongoing use of Prenatal BACs-on-Beads™ . METHODS: Some 1653 samples were analyzed. All results were confirmed by conventional karyotyping or another appropriate technique. All indications for invasive prenatal diagnosis were included. Amniotic fluid and chorionic villus samples were analyzed in equivalent proportions. RESULTS: The failure rate was 3.3% and the overall abnormality detection rate was ~1/10. Eighty-five percent of the detected abnormalities were common aneuploidies. Eleven microdeletions and duplications were identified, thus giving an overall yield for microdeletion and microduplication detection of 1/145. Compared with QF-PCR, Prenatal BACs-on-Beads™ provides an additional detection rate of ~1/250 for low-risk pregnancies. The false positive and negative rates were both <1%. CONCLUSION: When associated with conventional karyotyping, the Prenatal BACs-on-Beads™ assay combines a short turnaround time (typical of rapid aneuploidy detection tests) with valuable detection of the most frequent microdeletion syndromes that cannot be detected in cytogenetic analyses.
Asunto(s)
Amniocentesis/métodos , Líquido Amniótico/citología , Aneuploidia , Muestra de la Vellosidad Coriónica/métodos , Trastornos de los Cromosomas/diagnóstico , Cromosomas Artificiales Bacterianos/genética , Adulto , Líquido Amniótico/química , Trastornos de los Cromosomas/genética , Errores Diagnósticos/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Sangre Fetal/química , Sangre Fetal/citología , Edad Gestacional , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Técnicas de Diagnóstico Molecular , Embarazo , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
We report a boy with severe developmental delay, microcephaly and characteristic facial dysmorphism consisting in round face, hypertelorism, upslanted palpebral fissures, small nose, large mouth, micrognathia, sparse hair and eyelashes. Array-CGH revealed a de novo duplication of 103 kb within 17q21.2 not reported to date. The duplication includes 8 genes: DHX58, KAT2A, HSPB9, RAB5C, KCNH4, HCRT, GHDC and STAT5B. Three genes (KATA2, KCNH4, and STAT5B) may contribute to intellectual deficiency. Further observations will be necessary to confirm the specificity of the facial Gestalt.