According to the recent literature, UPD molecular studies should be performed in the following cases during prenatal diagnosis:

a) When mosaicism for chromosomes 6, 7, 11, 14, 15 and 16 is detected after chorionic villus sampling (CVS) and subsequent amniocentesis shows a normal fetal karyo­type, most likely caused by “trisomy rescue”. Theoreti­cally, in one-third of these cases UPD should be present in the euploid cell lines. For chromosome 20, evidence has accumulated during the past few years that it may be re­sponsible for abnormalities, when both chromosomes 20 are maternally derived, and it is advisable to offer UPD analysis [11,13,14]. For chromosomes 2, 4 and 5, there is still no convincing evidence that UPD may cause abnor­malities in order to justify molecular studies, when de­tected in a mosaic state in the placenta [5].

b) When a non homologous familial or de novo Robertsonian translocation involving chromosomes 14 and 15, known to contain imprinted genes, is detected either in CVS or amniotic fluid cells. According to Silverstein et al. [7], the risk estimate is 0.65%, which justifies UPD analysis in fetuses diagnosed prenatally with Roberstonian translocations. Based on this risk the same authors suggest testing these fetuses for UPD in amniocytes rather than chorionic villi, when the risk for unbalanced karyotype is ~1%, comparable to the risk for UPD.

c) When a homologous de novo Robertsonian trans­location or an isochromosome involving either chromo­some 14 or 15 is detected. Berend et al. [15] estimated that the risk of UPD, when a homologous acrocentric rear­rangement is identified prenatally, is approximately 66%, which certainly justifies UPD analysis.

d)   When a 47,+ESAC (extra structurally abnormal chromosome) karyotype is detected, it may infrequently coexist with UPD for the same chromosome that the ESAC was derived from; it may be that the zygote from a 23,abn + 23,N (46,abn) conception attempted to correct the imbalance, or at least lessen it, by replication of the normal homologue [16]. If the ESAC is derived from chro­mosome 15, known to contain imprinted genes, it is advis­able to perform UPD analysis.

Table 2. Uniparental disomy and associated genetic disease.