Delineating the Mosaic Trisomy 15 Phenotype Using a Serendipitous Mechanism as a Clue.

Parental balanced translocation is one of the traditional indications for invasive prenatal diagnosis. Usually, the diagnostic process is straightforward. Sometimes, however, results are not entirely clear and may reveal unexpected biological processes. We performed chorionic villi sampling for a paternal 8;15 reciprocal translocation in the sixth pregnancy of a Caucasian woman. Cytogenetic analysis of chorionic villi, after both short- and long-term cultures, revealed the presence of the same rearrangement found in the father as well as a trisomy 15. Surprisingly, the trisomy, which was initially expected to derive from aberrant segregation during paternal meiosis, resulted instead from maternal nondisjunction. Although a sonogram of the fetus appeared to be normal, follow-up amniocentesis demonstrated a low-level mosaic trisomy 15 in cells extracted from the amniotic fluid, while 10% of cells from fetal tissues sampled after termination of the pregnancy were also found to be trisomic. Fetal autopsy showed dysmorphic features, confirming the diagnosis of mosaic trisomy 15 and enabled deeper insight into the prenatal phenotype of this rare condition.

408 kb 15q11.2 microduplication by array comparative genomic hybridization in a fetus presenting with exomphalos, micrognathia, tetralogy of Fallot and normal karyotype: a genetic counseling dilemma in paternal carrier status.

Exomphalos may be associated with chromosomal abnormalities and syndromes. Severe exomphalos (herniation of liver, midgut and spleen) associated with increased nuchal translucency was seen at first trimester screening test. Karyotype by chorionic villus sampling showed normal male fetus. Follow up scan at 16 and 18 weeks of gestation confirmed the severe exomphalos and detected micrognathia and tetralogy of Fallot. Array comparative genomic hybridization (a-CGH) further demonstrated a 408 kb 15q11.2 microduplication, with the father-to-be as healthy carrier. This is the first case of an association between 15q11.2 micorduplication and fetal sonographic anomalies. Genetic counseling for estimation of recurrent risk of congenital anomalies is discussed.