Identification of uniparental disomy following prenatal detection of Robertsonian translocations and isochromosomes

Rearrangements of the acrocentric chromosomes (Robertsonian translocations and isochromosomes) are associated with an increased risk, of aneuploidy. G iven this, and the large number of reported cases of uniparental disomy (UP D) associated with an acrocentric rearrangement, carriers are presumed to b e at risk for UPD. However, an accurate risk estimate for UPD associated wi th these rearrangements is lacking. A total of 174 prenatally identified ac rocentric rearrangements, including both Robertsonian translocations and is ochromosomes, were studied prospectively to identify UPD for the chromosome s involved in the rearrangements. The overall goal of the study was to prov ide an estimate of the risk of UPD associated with nonhomologous Robertsoni an translocations and homologous acrocentric rearrangements. Of the 168 non homologous Robertsonian translocations studied, one showed UPD for chromoso me 13, providing a risk estimate of 0.6%. Four of the six homologous acroce ntric rearrangements showed UPD, providing a risk estimate of 66%. These ca ses have also allowed delineation of the mechanisms involved in producing U PD unique to Robertsonian translocations. Given the relatively high risk fo r UPD in prenatally identified Robertsonian translocations and isochromosom es, UPD testing should be considered, especially for cases involving the ac rocentric chromosomes 14 and 15, in which UPD is associated with adverse cl inical outcomes.