Clinical Information

Uniparental disomy (UPD) occurs when a child inherits 2 copies of a chromosome from 1 parent and no copies of that chromosome from the other parent. This error in division occurs during the formation of egg or sperm cells (meiosis). When an error causing UPD occurs during meiosis I both chromosome homologs from a single parent are transmitted, and heterodisomy results. When the error causing UPD occurs during meiosis II or as a postzygotic event, and a single parental homolog is transmitted to offspring in duplicate, isodisomy results. Meiotic recombination events within the context of UPD often result in a mixture of heterodisomy and isodisomy. UPD can involve an entire chromosome or only a segment. Mosaicism for UPD also occurs in combination with either chromosomally normal or abnormal cell lines.

When UPD occurs, the imbalance of maternal versus paternal genetic information for the involved chromosome can be associated with clinical symptoms in the affected child. UPD does not always impart an abnormal clinical phenotype however. In fact, while isodisomy can result in disease due to a recessive allele at any location, heterodisomy is not expected to result in an abnormal clinical phenotype unless the involved chromosome or chromosomal segment includes imprinted genes. Imprinted genes demonstrate differential expression depending on parent of origin. Disorders that result from UPD of imprinted genes are not due to a defect in the imprinting mechanism itself, but rather they are due to an unbalanced parental contribution of normally imprinted alleles that results in altered expression of imprinted genes. For example, when maternal UPD 15 occurs (2 copies of the maternal chromosome 15 instead of 1 maternal and 1 paternal copy of chromosome 15), it causes Prader-Willi syndrome due to the lack of paternally expressed genes at the imprinted site.

UPD has been described for many but not all chromosomes. In addition to the rare cases of autosomal recessive disease that result from isodisomy, clinical syndromes associated with UPD have been described for only a few chromosomes, including Russell-Silver syndrome (UPD 7), Prader-Willi syndrome (UPD 15), Angelman syndrome (UPD 15), transient neonatal diabetes (UPD 6), and UPD of chromosome14.

UPD cannot be identified by gross cytogenetic analysis and requires DNA-based analysis using multiple polymorphic markers spanning the chromosome of interest. Specimens from both parents and the child or fetus are required.