RESUMEN
OBJECTIVE: With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. METHODS: The Belgian MicroArray Prenatal (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. RESULTS: In this three-year period, 13 266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs, 31.5% would have remained undetected with non-invasive prenatal test as the first-tier test. CONCLUSION: The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype-phenotype correlation.
Asunto(s)
Aberraciones Cromosómicas , Anomalías Congénitas/genética , Variaciones en el Número de Copia de ADN/genética , Haploinsuficiencia/genética , Análisis por Micromatrices/métodos , Adulto , Artrogriposis/diagnóstico , Artrogriposis/genética , Bélgica , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/genética , Hibridación Genómica Comparativa , Anomalías Congénitas/diagnóstico , Bases de Datos Genéticas , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Femenino , Predisposición Genética a la Enfermedad , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , Ictiosis Ligada al Cromosoma X/diagnóstico , Ictiosis Ligada al Cromosoma X/genética , Cariotipificación , Embarazo , Diagnóstico PrenatalRESUMEN
After their successful introduction in postnatal testing, genome-wide arrays are now rapidly replacing conventional karyotyping in prenatal diagnostics. While previous studies have demonstrated the advantages of this method, we are confronted with difficulties regarding the technology and the ethical dilemmas inherent to genomic arrays. These include indication for testing, array design, interpretation of variants and how to deal with variants of unknown significance and incidental findings. The experiences with these issues reported in the literature are most often from single centres. Here, we report on a national consensus approach how microarray is implemented in all genetic centres in Belgium. These recommendations are subjected to constant re-evaluation based on our growing experience and can serve as a useful tool for those involved in prenatal diagnosis.
Asunto(s)
Hibridación Genómica Comparativa/métodos , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Diagnóstico Prenatal/métodos , Bélgica , Consenso , Femenino , Humanos , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
Interstitial duplications of the short arm of chromosome 2 have been rarely described. Here, we report on two unrelated patients with overlapping chromosome 2p16 â p22 de novo microduplications found by SNP-array analysis. The affected individuals were an 8-year-3-month-old boy with a direct duplication of approximately 14.6 Mb harboring 63 genes, and a 12-year-old girl with a direct duplication of around 9.6 Mb harboring 48 genes. Both patients have severe growth retardation, delayed bone age, prominent veins on trunk and extremities, total IGF1 level in the low range, mild developmental delay, and facial dysmorphism such as relative macrocephaly, a broad and prominent forehead, and a large anterior fontanelle. Comparison with patients previously reported in the literature and in the DECIPHER 5.1 and ECARUCA databases indicates a common region of interest of around 1.9 Mb responsible for most of the features. Two candidate genes (EPAS and RHOQ), may be particularly relevant for the marked growth retardation and developmental delay.
