Biomedical Engineering Reference
In-Depth Information
Angelman syndrome
Prader-willi syndrome
Maternal deletion
15q11 - q13
Paternal uniparental
disomy
Paternal deletion
15q11 - q13
Maternal uniparental
disomy
Paternal
Maternal
7. 1 6
Angelman and Prader-Willi syndromes. Notice that both
syndromes are characterized by a deletion of chromosome 15 at
band q11-q13. Differences in the symptoms of the patient and thus
the syndrome present are determined by whether the deletion is
maternally (Angelman) or paternally (Prader-Willi) inherited. (Image
created by Kamila Dabrowski, St Peter's University, Art Department,
Graphic Arts, Jersey City, NJ.)
phenotypes share the same microscopically visible cytogenetic deletion at
15q11. However, Prader-Willi is characterized by obesity and mental retar-
dation, while Angelman is characterized by mental retardation, ataxia, lack
of speech and seizures.
It was not until the discovery of a very large family that had both
Prader-Willi and Angelman syndrome segregating together that the salient
clue to this mystery of the same microscopic deletion causing two very
dissimilar diseases was uncovered. In this pedigree it was found that in
Prader-Willi cases, the source of the deletion was always paternal, while in
Angelman, cases that have the same deleted 15q11 region, the deletion is
always maternally inherited. The differences between the two phenotypes
were related to the sex of the parent. At the molecular level, this phenom-
enon turned out to be due to the lack of expression of imprinted gene(s)
from the maternally inherited chromosome in Prader-Willi, and a lack of
expression of closely linked but different paternally imprinted gene(s) in
the same chromosome region in Angelman syndrome. Since the normal sit-
uation for genes in this imprinted area is to have only one active copy of
these genes, in both syndromes the deletion removes the chromosomal area
that normally expresses these genes so there is no genetically active copy of
these genes in the cell having the deletion.
It was further discovered that there was another mechanism to get these
two syndromes - a process called
uniparental disomy
. This is a phenomenon
