Inheritance - parental disomy

Definition

Uniparental disomy (UPD) - an individual inherits both copies of a chromosome (or chromosome segment) from a single parent, rather than one from each parent - clinically significant specifically when the chromosome involved carries imprinted genes, or when it unmasks a recessive condition
Rare overall, but a well-recognised mechanism underlying a proportion of Prader-Willi syndrome, Angelman syndrome, and some cases of unexplained recessive disease presentation

UPD typically arises from a trisomy rescue event - a conceptus starts with three copies of a chromosome (a meiotic error), and the cell line loses one copy to restore the normal number of two, but by chance retains both remaining copies from the same parent rather than one from each
Clinical consequences depend entirely on which chromosome is involved: UPD of an imprinted-gene-containing chromosome (e.g. chromosome 15) produces a specific imprinting-related phenotype (Prader-Willi or Angelman syndrome, depending on which parent's chromosome is duplicated); UPD of a chromosome carrying a recessive disease gene can unmask recessive disease from only one carrier parent (since both copies now derive from that single carrier), rather than requiring two carrier parents as in standard recessive inheritance

Suspected when a child has features of an imprinting disorder (e.g. Prader-Willi/Angelman phenotype) but standard deletion testing is negative, or when a child has an unexplained recessive condition with only one identified carrier parent
Specific UPD testing (comparing parental and child genotypes across the chromosome in question) is required - it is not detected by standard karyotype or most routine sequencing approaches

Recurrence risk for UPD is generally low (it typically arises as a sporadic meiotic error) - an important, often reassuring point for genetic counselling once UPD is confirmed as the mechanism, in contrast to a primary imprinting-centre defect (which can carry a higher recurrence risk)

Prader-Willi syndrome, Angelman syndrome, unexplained apparent recessive disease with only one carrier parent identified

UPD is a recognised, if uncommon, explanation when standard genetic testing does not fit the expected inheritance pattern (e.g. only one carrier parent found for an apparently recessive condition) - it should be considered specifically in this scenario rather than assuming the second, unidentified carrier parent was simply missed

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