Uniparental disomy (UPD) refers to a condition in which an individual has inherited both copies (alleles) or parts of a chromosome from only one parent. It is called isodisomy if the same parental chromosome is duplicated or heterodisomy if the two different copies of a chromosome derive from only one parent. In the majority of chromosomes, this condition has most likely no pathological significance. However, if a variant in a recessive gene is present on the chromosome that is inherited as an isodisomy, it is homozygous in the offspring due to duplication of this chromosome or gene and causes the disease. Alternatively, if a chromosome or chromosomal region contains genes that are affected by genomic imprinting, i.e. that are active or inactive depending on the parental origin, is inherited, this may lead to complications. This plays a role in Prader-Willi syndrome or Angelman syndrome. UPD diagnostics also has a functional significance in the context of prenatal diagnostics, e.g. if a mosaic is present in the chorionic villus sampling for a trisomy of one of the chromosomes known to have pathological effects of UPD. In this case, it is necessary to investigate whether UPD has occurred in the unborn child by, for instance, “trisomy correction”. If the initial zygote was trisomic, i.e. it carried two chromosomes of the same type from one parent and one chromosome from the other parent, a “trisomy correction” can also result in loss of the single chromosome copy of one parent. The two chromosomes of the other parent remain which suggests a normal condition but may have pathological effects.
Robertsonian translocations involving chromosomes 14 and 15 also require prenatal diagnostics to exclude UDP, although the risk is most likely less than 1%. Apart from the chromosomes listed below, in which an UPD can cause a disease, the literature also provides evidence for chromosomes 2, 3, 16 and 20. Therefore, if a trisomy is present, even in mosaic form, a prenatal diagnosis should exclude an UPD.
The most common disorders caused by UPD:
- 6q23-24, paternal, transient neonatal diabetes mellitus
- 7p11-13, maternal, Silver-Russell syndrome, primordial short stature (also chromosome 11)
- 11p15.5, paternal (in mosaic form), Beckwith-Wiedemann syndrome (EMG syndrome)
- 14, paternal, intrauterine growth retardation, malformations, severe developmental delay
- 14, maternal, pre- and postnatal growth retardation, mild developmental delay, dysmorphic signs
- 15q11-13, maternal, Prader-Willi syndrome
- 15q11-13, paternal, Angelman syndrome
Eggermann T et al. 2015, Trends Mol Med 21(2):77 / Kotzot 2008, J Med Genet 45:545 / Kotzot 2008, Ultrasound Obstet Gynecol 31:100 / Engel 2006, Eur J Hum Genet 14:1158 / Kotzot 2002, Am J Med Genet 111:366 / Buiting et al. 2001, Medizinische Genetik 13:124