Prader–Willi and Angelman syndromes

Prader–Willi and Angelman syndromes are caused by
distinct genes within the 15q11-13 region that are subject to
different imprinting. The Prader–Willi gene is only active on
the chromosome inherited from the father and the Angelman
syndrome gene is only active on the chromosome inherited
from the mother. Similar de novo cytogenetic or molecular
deletions can be detected in both conditions. Prader–Willi
syndrome occurs when the deletion affects the paternally
derived chromosome 15, whereas the Angelman syndrome
occurs when it affects the maternally derived chromosome. In
most patients with Prader–Willi syndrome who do not have a
chromosome deletion, both chromosome 15s are maternally
derived (uniparental disomy). When UPD involves imprinted
regions of the genome it has the same effect as a chromosomal
deletion arising from the opposite parental chromosome. In
Prader–Willi syndrome both isodisomy (inheritance of identical
chromosome 15s from one parent) and heterodisomy
(inheritance of different 15s from the same parent) have been
observed. Uniparental disomy is rare in Angelman syndrome,
but when it occurs it involves disomy of the paternal
chromosome 15. Other cases are due to mutations within the
Angelman syndrome gene (UBE3A) that affect its function.