Complex and segmental uniparental disomy updated

Objective: To review all cases with segmental and/ or complex uniparental disomy (UPD) and to discuss the impact of these cases on medical genetics. Design: Searching for published reports in PubMed and in the abstract books of the annual meetings of the American Society of Human Genetics and the European Society of Human Genetics up to March 2008. Results: In total, 26 cases with segmental UPD and a normal karyotype, 38 cases with UPD of a whole chromosome and a simple reciprocal or non- homologous Robertsonian translocation, four cases each with two isochromosomes and UPD of the short arm isochromosome and opposite UPD of the long arm isochromosome, three cases with UPD and an isochromosome of the short arm and the long arm of a metacentric or a submetacentric chromosome, one case with maternal UPD and an isochromosome 8 associated with a homozygous deletion (8)(p23.3pter), 42 cases with UPD and an isochromosome of the long arm of an acrocentric chromosome, 33 cases with UPD and a supernumerary marker or ring chromosome, 17 cases with UPD of a whole or parts of a chromosome and a complex karyotype, 13 cases with most likely mosaicism for genome wide paternal UPD, and three cases with most likely mosaicism for genome wide maternal UPD were found. Conclusion: This update shows that, in particular, the number of reported cases with segmental UPD or UPD associated with a marker chromosome clearly increased within the last few years, and that the investigation of both parents in cases with homozygosity of an autosomal recessively inherited mutation in some cases might help improve genetic counselling, resulting in a reduced recurrence risk in the case of UPD. Moreover, cases with segmental or complex UPD show that meiosis and early postzygotic mitoses seem to be more complex events than previously thought. For the formation of all kinds of segmental or complex UPD or genome wide UPD mosaicism, always a fortunate co- occurrence of meiotic or mitotic recombination, abnormal segregation, and subsequent correction are necessary. No case of recurrence has been reported until now. Therefore, in subsequent pregnancies invasive prenatal diagnosis is not necessarily indicated.