RESUMEN
It is estimated that 10-15 % of all clinically recognised pregnancies results in a miscarriage, most of which occur during the first trimester. Large-scale chromosomal abnormalities have been found in up to 50 % of first-trimester spontaneous abortions and, for several decades, standard cytogenetic analysis has been used for their identification. Recent studies have proven that array comparative genomic hybridisation (array-CGH) is a useful tool for the detection of genome imbalances in miscarriages, showing a higher resolution, a significantly higher detection rate and overcoming problems of culture failures, maternal contamination and poor chromosome morphology. In this study, we investigated the possibility that submicroscopic chromosomal changes, not detectable by conventional cytogenetic analysis, exist in euploid miscarriages and could be causative for the spontaneous abortion. We analysed with array-CGH technology 40 foetal tissue samples derived by first-trimester miscarriages with a normal karyotype. A whole-genome microarray with a 100-Kb resolution was used for the analysis. Forty-five copy number variants (CNVs), ranging in size between 120 Kb and 4.3 Mb, were identified in 31 samples (24 gains and 21 losses). Ten samples (10/31, 32 %) have more than one CNV. Thirty-one CNVs (68 %) were defined as common CNVs and 14 were classified as unique. Six genes and five microRNAs contained within these CNVs will be discussed. This study shows that array-CGH is useful for detecting submicroscopic CNVs and identifying candidate genes which could account for euploid miscarriages.
Asunto(s)
Aborto Espontáneo/genética , Hibridación Genómica Comparativa/métodos , Aberraciones Cromosómicas , Bandeo Cromosómico , Cromosomas/ultraestructura , Femenino , Dosificación de Gen , Variación Genética , Genoma Humano , Humanos , Cariotipificación , Embarazo , Primer Trimestre del EmbarazoAsunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Compuestos Bicíclicos con Puentes/uso terapéutico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Enfermedades de los Genitales Femeninos/cirugía , Complicaciones del Trabajo de Parto/tratamiento farmacológico , Parasimpatolíticos/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Espasmo/tratamiento farmacológico , Método Doble Ciego , Evaluación de Medicamentos , Femenino , Humanos , EmbarazoRESUMEN
We report making the prenatal diagnosis of thanatophoric dysplasia without "cloverleaf" skull at 21 weeks gestation. The ultrasound examination showed short and bowed limbs, narrow thorax, and large head. Radiological and histological studies confirmed the aborted fetus to be affected with thanatophoric dysplasia. The differential prenatal diagnosis with other skeletal dysplasias is discussed.