Clinical follow up of uniparental disomy 16: First data

Following the introduction of the concept of uniparental disomy (UPD) in 1980 by Engel this segregational anomaly is reported in an ever increasing number of patients. So far, several groups of individuals with an increased risk for UPD have been identified including abnormal carriers of familial balanced translocations or centric fusions, carriers of mosaic trisomies, and fetuses after prenatal diagnosis of confined placental mosaicism. A major pathogenetic mechanism appears to be post-meiotic chromosome loss in trisomic conceptuses. UPD was repeatedly observed in the fetus after diagnosis of mosaic or non-mosaic trisomies in the placenta which are usually considered {open_quotes}lethal{close_quotes} (i.e. trisomies 15 and 16). In an ongoing study to determine the incidence and clinical consequences of UPD we investigated the parental origin of chromosomes in the disomic cell line after prenatal diagnosis of mosaicism for various trisomies (e.g. 2, 7, 14, 15, and 16). At present, two maternal disomies 16 and one maternal disomy 15 were identified. Severe intrauterine growth retardation was a common symptome which, however, was also present in some but not all mosaics with a biparental origin of the chromosomes in question. While prognosis is clear in some instances (i.e. UPD 15) counseling can be extremely difficultmore » in others, when imprinting effects and homozygosity for unknown recessive traits present in a parent have to be considered. To assess the clinical significance, detailed follow-up studies of proven cases of uniparental disomies are essential. First data of two cases with UPD 16 are presented.« less