Uniparental disomy and Robertsonian translocations: risk estimation and prenatal testing

Uniparental disomy (UPD) is defined by the inheritance of both homologous chromosomes from only one parent, resulting in an imbalance of the expression of imprinted genes. With the recent identification of several diseases associated with UPD, the diagnostic significance of this molecular finding is a focus of interest. Acrocentric chromosomes involved in Robertsonian translocations (RTs) are particularly prone to being affected by mis-segregation events, possibly resulting in UPD. While UPDs of chromosomes 13, 21, and 22 have no clinical consequences, and therefore have no diagnostic impact despite of homozygosity of recessive alleles, prenatal testing for UPDs 14 or 15 is becoming increasingly asked for.

Thirty-one fetuses with nonhomologous balanced RTs involving chromosome 14 were tested for UPD14 by microsatellite typing.

No cases of maternal UPD14 were detected among the 31 fetuses analyzed.

Based on our own data from molecular testing in 31 prenatal RT cases and findings in the published literature, we delineated a risk of 0.3% for a UPD with clinical consequences for prenatally detected carriers of a nonhomologous RT. Prenatal UPD testing is not associated with any additional risk to the pregnancy once invasive prenatal testing has been carried out. However, the possibly conflicting consequences in the case of a prenatal UPD identification should be discussed in advance. Furthermore, risk figures in specific clinical cohorts, such as couples prior to intracytoplasmic sperm injection, as well as questions of prenatal diagnostic management, will be discussed.