Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi syndrome

Abstract

We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo jumping translocation of distal chromosome 15q, resulting in partial trisomy for 15q24-qter. A maternal uniparental heterodisomy for chromosome 15 was present in all cells, defining the molecular basis for the PWS in this patient. The translocated distal 15q fragment was of paternal origin and was present as a jumping translocation, involving three different translocation partners, chromosomes 14q, 4q, and 16p. The recipient chromosomes appeared cytogenetically intact and interstitial telomere DNA sequences were present at the breakpoint junctions. This strongly suggests that the initial event leading to the translocation of distal 15q was a non-reciprocal translocation, with fusion between the 15q24 break-point and the telomeres of the recipient chromosomes. These observations are best explained by a partial zygotic trisomy rescue and comprise a previously undescribed mechanism leading to partial trisomy.

Full text

J7Med
Genet
1997;34:395-399
Trisomy
15
rescue
with
jumping
translocation
of
distal
1
5q
in
Prader-Willi
syndrome
Koenraad
Devriendt,
Paul
Petit,
Gert
Matthijs,
Joris
R
Vermeesch,
Maureen
Holvoet,
Alain
De
Muelenaere,
Peter
Marynen,
Jean-Jacques
Cassiman,
Jean-Pierre
Fryns
Abstract
We
report
a
patient
with
Prader-Willi
syndrome
(PWS)
and
mosaicism
for
a
de
novo
jumping
translocation
of
distal
chro-
mosome
15q,
resulting
in
partial
trisomy
for
15q24-qter.
A
maternal
uniparental
heterodisomy
for
chromosome
15
was
present
in
all
cells,
defining
the
molecular
basis
for
the
PWS
in
this
patient.
The
translocated
distal
15q
fragment
was
of
paternal
origin
and
was
present
as
a
jumping
translocation,
involving
three
different
translocation
partners,
chromo-
somes
14q,
4q,
and
16p.
The
recipient
chromosomes
appeared
cytogenetically
intact
and
interstitial
telomere
DNA
se-
quences
were
present
at
the
breakpoint
junctions.
This
strongly
suggests
that
the
initial
event
leading
to
the
translocation
of
distal
15q
was
a
non-reciprocal
transloca-
tion,
with
fusion
between
the
15q24
break-
point
and
the
telomeres
of
the
recipient
chromosomes.
These
observations
are
best
explained
by
a
partial
zygotic
trisomy
rescue
and
comprise
a
previously
unde-
scribed
mechanism
leading
to
partial
trisomy.
(JMed
Genet
1997;34:395-399)
Keywords:
Prader-Willi
syndrome;
jumping
transloca-
tion;
uniparental
disomy;
partial
trisomy
Centre
for
Human
Genetics,
University
Hospital
Leuven,
Herestraat
49,
B-3000
Leuven,
Belgium
K
Devriendt
P
Petit
G
Matthijs
J
R
Vermeesch
M
Holvoet
P
Marynen
J-J
Cassiman
J-P
Fryns
MPIOLV
ter
Engelen,
Klerken,
Belgium
A
De
Muelenaere
Correspondence
to:
Dr
Devriendt.
Received
5
August
1996
Revised
version
accepted
for
publication
13
December
1996
Prader-Willi
syndrome
(PWS)
is
caused
by
the
absence
of
a
paternal
genetic
contribution
to
chromosomal
region
15ql
1-13,
either
through
deletion
on
the
paternal
chromosome
or
through
the
presence
of
maternal
uniparental
disomy
for
chromosome
15
(UPD
15
mat).'
2
Other
chromosomal
aberrations
have
been
reported
in
PWS,
such
as
unbalanced
translo-
cations
or
a
marker
chromosome
derived
from
chromosome
15,
resulting
in
either
a
deletion
in
paternal
chromosome
15ql
1-13
or
in
UPD15
mat.9
Jumping
translocations
are
extremely
rare
and
describe
the
translocation
of
the
same
chromosomal
fragment
to
different
translocation
partners
in
different
cell
lines
of
a
single
person.
Interestingly,
the
initial
descrip-
tion
of
a
jumping
translocation
was
also
in
a
patient
with
PWS."'
The
majority
of
jumping
translocations
reported
so
far
involve
hetero-
chromatic
chromosomal
regions,
such
as
telo-
meres,
centromeres,
or
satellites."
Rarely,
jumping
translocations
with
an
interstitial
breakpoint
in
one
of
the
chromosomes
have
been
reported
and,
interestingly,
most
of
these
cases
were
patients
with
the
PWS,
with
a
breakpoint
in
chromosomal
region
15ql
1-13.4
We
report
here
a
patient
with
Prader-Willi
syndrome
carrying
a
jumping
translocation
resulting
in
a
partial
trisomy.
Subjects
and
methods
CLINICAL
DATA
The
patient
is
a
girl,
the
third
child
of
healthy,
non-consanguineous
parents.
Family
history
is
negative
with
regard
to
mental
retardation
or
congenital
malformations.
At
the
time
of
birth,
the
mother
was
25
and
the
father
29
years
old.
During
pregnancy,
fetal
movements
were
reduced
and
there
was
polyhydramnios.
She
was
born
at
term
with
a
birth
weight
of
2200
g
(3rd
centile=2500
g).
The
neonatal
period
and
infancy
were
characterised
by
severe
hypotonia
and
major
feeding
difficulties,
necessitating
frequent
hospital
admission
and
nasogastric
tube
feeding.
Weight
gain
was
poor.
Around
the
age
of
2
years,
she
developed
a
marked
change
in
feeding
behaviour,
with
an
increase
in
appetite.
This
led
to
the
gradual
develop-
ment
of
obesity
during
childhood.
At
the
age
of
22
months,
weight
was
10
kg
(3rd-25th
centile),
height
85
cm
(50th
centile),
and
head
circumference
46
cm
(3rd-25th
centile).
At
the
age
of
10
years,
weight
was
42.5
kg
(90th-97th
centile),
height
135
cm
(25th-50th
centile),
and
head
circumference
52
cm
(25th-50th
centile).
She
suffered
from
recurrent
urinary
infections
and
at
the
age
of
2
years
unilateral
vesicoureteral
reflux
was
surgically
corrected.
Psychomotor
development
was
severely
de-
layed:
she
could
sit
at
2.5
years
and
walk
at
3
years.
First
words
appeared
at
8
years.
Now,
at
the
age
of
22
years,
there
is
truncal
obesity,
with
weight
73.5
kg
(90th-97th
centile),
height
153
cm
(3rd-25th
centile),
and
head
circum-
ference
55
cm
(75th
centile).
She
is
dysmor-
phic,
with
short
hands
(hand
length
15.5cm
and
finger
length
6.5
cm,
both
below
the
3rd
centile)
and
short
feet,
low
set
ears,
and
almond
shaped
eyes
(fig
1).
The
saliva
is
sticky
and
the
teeth
are
carious.
There
is
no
hypopig-
mentation.
The
corners
of
the
mouth
are
downturned
and
the
palate
is
high
arched.
She
is
myopic.
There
is
hypotonia,
with
genu
valgum
and
dorsal
kyphosis.
She
is
severely
mentally
retarded
and
exhibits
obsessive
be-
haviour,
temper
tantrums,
and
skin
picking.
Sleep
is
disturbed,
with
frequent
awakening.
There
is
primary
amenorrhoea.
She
forages
food.
Pain
sensitivity
is
diminished.
She
fulfils
all
major
and
seven
minor
criteria
of
the
395
group.bmj.com on July 13, 2011 - Published by jmg.bmj.comDownloaded from

Devriendt
et
al
Wl.
Figure
2
G
banlded
parti'al
karyotype
showinlg,from
left
to
right,
chromosomes
4,
14,
15,
and
16.
Note
the
4q+,
14q+,
and
16p+
(arrowheads).
This
fragmeint
was
tentatively
identified
as
15q24-qter.
I
...i;
....
.
$
.. i l
fl
:;3
.f
..
: .
::
. . t
c;.
........
,
$;-1
N
S
.. .... .. .........
.....
....
.........
tg
Figure
I
Clinicalfeatures
of
the
patient
at
22
years.
Note
the
truncal
obesity,
short
stature,
sm
all
hands
and
feet,
and
hypotonia,
with
downturned
corners
of
the
mouth.
recently
proposed
diagnostic
criteria
for
Prader-Willi
syndrome.'2
METHODS
Cytogenetic
analysis
Chromosome
studies
on
peripheral
lym-
phocytes
and
skin
fibroblasts
were
performed
according
to
standard
cytogenetic
techniques,
and
karyotyping
was
by
Giemsa
banding.
Fluorescent
in
situ
hybridisation
(FISH)
and
detection
were
carried
out
using
coatasome
15
chromosome
paint
and
SNRPN/PML
probes,
obtained
from
ONCOR
(Gaithersburg,
MD).
The
PML
probe
supplied
together
with
the
SNRPN
probe
is
present
as
a
control
probe
and
recognises
sequences
in
15q22.
A
biotin
labelled
FES
cosmid
probe
(15q26.1)
(a
gift
from
E
Schoenmakers,
Leuven)
and
oligonu-
cleotide
(TTAGGG)7
probes
were
applied
as
described
by
Pinkel
et
al'3
and
Vermeesch
et
al"
respectively.
Pictures
were
taken
by
digital
imaging
microscopy
using
a
cooled
charge
coupled
device
camera
system
(Photometrics).
Merging
and
pseudocolouring
were
performed
using
the
SmartCapture
software
(Vysis,
Stutt-
gart,
Germany).
At
least
30
metaphases
were
examined
with
each
probe.
Molecular
analysis
Genomic
DNA
was
extracted
from
peripheral
white
blood
cells
and
cultured
fibroblasts
and
analysed
by
Southern
blotting
using
probes
Table
I
Distribution
of
the
different
karyotypes
Karvotype
46,XX
46,XX,4q+
46,XX,14q+
46,XX,16p+
Total
Lymphocytes
(No
of
cells)
8
11
85
3
107
Fibroblasts
(No
of
cells)
51
14
35
0
100
PW7
1'5
(a
gift
from
Dr
B
Horsthemke)
and
DN34E
as
previously
described.'6
Analysis
of
polymorphic
microsatellite
mark-
ers
was
done
using
PCR
amplification
on
the
patient
(white
blood
cells
and
fibroblasts)
and
her
mother
(white
blood
cells).
DNA
from
the
father
was
not
available.
The
following
loci
on
chromosome
15
were
examined:
D15S122,
D15S165,
APW,
D15S123,
FES,
D15S107,
and
D115S120.
The
primer
sequences
were
obtained
from
GDB.
Results
CYTOGENETIC
ANALYSIS
Cytogenetic
analysis
on
both
lymphocyte
and
fibroblast
tissues
showed
a
normal
46,XX
cell
line
and,
in
addition,
unbalanced
karyotypes
with
partial
trisomy
15q24-qter
(table
1,
fig
2).
Mosaicism
consistent
with
a
jumping
translo-
cation
was
observed
with
a
predominant
46,XX,14q+
cell
line
as
well
as
46,XX,4q+
and
46,XX,16p+
cell
lines
(table
1,
fig
2).
Chromosome
painting
with
a
chromosome
15
specific
probe
confirmed
that
the
extra
chro-
mosomal
material
originated
from
chromo-
some
15
(fig
3A).
FISH
using
a
cosmid
probe
for
the
FES
gene,
located
on
chromosome
15q26.
1,
showed
three
signals
in
all
unbal-
anced
metaphases,
one
on
the
distal
region
of
each
chromosome
15
and
one
on
the
extra
material
translocated
onto
chromosomes
14q,
4q,
and
16p
(fig
3B).
FISH
using
the
SNRPN/
PML
cocktail
probe
showed
normal
signals
at
15ql
1
and
15q22
on
both
chromosomes,
excluding
a
deletion
involving
the
SNRPN
gene
(fig
3C).
This
also
confirmed
that
the
translocated
region
in
the
unbalanced
cells
originated
from
the
distal
15q
region,
with
a
breakpoint
located
between
15q22
(PMLcon-
trol
probe)
and
15q26.1
(FES
locus).
The
karyotypes
of
the
parents
and
sibs
were
normal
after
G
banding.
PARENTAL
ORIGIN
OF
THE
CHROMOSOMES
15
AND
TRANSLOCATED
FRAGMENT
DISTAL
1
5q
The
results
obtained
with
probes
DN34
and
PW71
showed
hypermethylation
of
the
PWS
region,
indicating
the
absence
of
a
paternal
allele
(not
shown).'5
56
This
is
compatible
with
UPD
15
mat.
A
submicroscopic
deletion
on
the
paternal
chromosome
15ql
1
gives
the
same
methylation
pattern,
but
this
was
excluded
by
FISH
using
a
cosmid
probe
from
the
SNRPN
gene
(fig
3C).
A
more
detailed
analysis
of
the
parental
origin
of
the
chromosomes
15
was
done
using
polymorphic
markers
distributed
along
this
chromosome.
Four
of
the
six
markers
analysed
were
informative
and
showed
that
the
patient
had
inherited
two
different
396
group.bmj.com on July 13, 2011 - Published by jmg.bmj.comDownloaded from

J7umping
translocation
in
Prader-Willi
syndrome
Figure
3
(A)
FISH
analysis
using
a
chromosome
15
painting
library.
Note
that
the
fragment
translocated
to
chromosome
l4qter
originated
from
chromosome
15.
(B)
FISH
analysis
with
cosmid
probe
FES
(located
on
chromosome
15q26).
Three
distinct
signals
were
present,
two
on
the
normal
chromosomes
15
and
one
on
the
distal
long
arm
of
chromosome
4,
at
the
site
of
the
translocatedfragment.
(C)
FISH
analysis
using
the
SNRPN/PML
cocktail
probe
showed
the
presence
of
normal
signals
at
15q1
1
and
15q22
on
both
chromosomes,
excluding
a
deletion
involving
the
SNRPN
gene.
Moreover,
the
breakpoint
on
chromosome
15q
must
be
located
between
PML
(15q22)
and
FES
(15q26).
Patient
WBC
Patient
skin
f
APW
FES
Mother
'-F
W
BC
Figure
4
Analysis
of
microsatellite
markers
APWand
FES.
DNA
from
the
patient's
peripheral
white
blood
cells
(top
row)
and
fibroblasts
(middle
row)
and
from
maternal
white blood
cells
(bottom
row)
was
used
for
PCR
amplification
of
the
polymorphic
repeats
APW
(dinucleotide
repeat)
and
FES
(tetranucleotide
repeat).
For
FES,
three
alleles
are
observed
for
the
patient,
two
of
which
are
inherited
from
the
mother,
while
the
third
must
be
of
paternal
origin
(arrowhead).
In
fibroblasts,
the
amount
of
the
paternal
allele
is
reduced,
reflecting
the
presence
of
mosaicism,
with
a
normal
46,XX
cellfibroblast
line.
maternal
chromosomes,
which
is
fully
compat-
ible
with
the
presence
of
maternal
heterodis-
omy
(fig
4,
other
results
not
shown).
However,
in
the
absence
of
paternal
DNA,
this
could
not
be
proven
with
absolute
certainty.
The
parental
origin
of
the
translocated
chro-
mosome
1
5q
fragment
was
determined
by
means
of
polymorphic
microsatellite
markers
in
1
5q26
to
1
5qter.
Analysis
of
the
polymor-
phic
marker
FES,
located
in
15q26,
detected
three
different
alleles,
both
in
skin
fibroblasts
and
in
peripheral
white
blood
cells
(fig
4).
One
of
the
alleles
was
not
present
in
the
mother
and
therefore
almost
certainly
represents
the
pater-
nal
allele.
Similarly,
for
marker
D1
5S107,
also
on
distal
1
5q,
an
allele
not
present
in
the
mother
was
found
in
the
patient.
This
is
in
contrast
to
the
markers
proximal
to
15q24,
where
no
alleles
absent
in
the
mother
could
be
found
(results
not
shown).
In
conjunction
with
the
cytogenetic
and
methylation
studies,
these
findings
are
fully
consistent
with
a
paternal
ori-
gin
of
the
translocated
fragment
of
distal
chro-
mosome
15q.
Dosage
analysis
of
the
microsatellite
markers
FES
and
D15S107
showed
that
the
paternal
allele
was
present
in
the
majority
of
white
blood
cells,
whereas
in
skin
fibroblasts
a
lower
dose
of
the
paternal
allele
was
found
compared
to
the
maternal
alleles
(fig
4).
This
is
in
agreement
with
the
cytogenetic
findings,
showing
a
partial
trisomy
for
distal
1
5q
in
the
majority
of
lymphocytes,
but
only
in
approximately
50%
of
fibroblasts
(table
1).
INTERSTITIAL
TELOMERE
SEQUENCES
AT
THE
BREAKPOINT
JUNCTION
SITES
The
distal
part
of
chromosome
1
5q
was
trans-
located
onto
three
different
chromosomes,
14q,
4q,
and
16p.
FISH,
using
a
telomere
probe,
showed
the
presence
of
two
signals
on
all
normal
chromosomes,
including
the
two
chromosomes
15.
On
the
chromosomes
14
and
4,
carrying
the
translocated
1
5q
fragment,
three
signals
were
detected,
two
at
the
telomeres
and
one
interstitial
signal
(fig
5).
These
interstitial
signals
coincided
with
the
junction
sites
between
the
translocated
distal
chromosome
15q
fragment
and
the
transloca-
tion
partners.
No
metaphases
with
a
1
6p+
could
be
analysed.
Discussion
The
patient
reported
here
fulfils
the
diagnostic
criteria
of
PWS
according
to
Holm
et
al,'2
with
the
presence
of
all
main
clinical
features
and
seven
minor
criteria.
By
conventional
cytoge-
netics,
mosaicism
consistent
with
a
jumping
translocation
of
distal
15q
and
resulting
in
a
partial
trisomy
for
distal
15q
was
detected
in
both
lymphocytes
and
in
fibroblasts.
This
rear-
rangement
must
have
occurred
de
novo
as
the
karyotypes
of
both
parents
were
normal.
Maternal
uniparental
heterodisomy
for
chro-
mosome
15
was
present,
explaining
the
PWS
phenotype.
This
was
shown
by
methylation
analysis
of
the
imprinted
region
on
chromo-
some
1
5ql
1
and
further
supported
by
the
analysis
of
polymorphic
microsatellite
markers,
distributed
along
chromosome
15.
On
top
of
397
group.bmj.com on July 13, 2011 - Published by jmg.bmj.comDownloaded from

Devriendt
et
al
Figure
5
FISH
analysis
with
a
telonmeric
probe.
Note
that
on7
the
derivative
chromosome
14,
with
the
extra
distal
15q
fragment,
three
signals
are
present,
two
at
the
ends
of
the
chromosomes
and
one
interstitial
(indicated
by
arrow)
at
the
translocation
junction
region.
2
47,XX,
1
5+
46,XX,UPD1
5mat,der(1
4q+)
46,XX,
U
PD1
5mat,der(4q+)
3~~~~
4\A
-3
^
46,XX,UPD1
5mat
Maternal
chromosome
15
Paternal
chromosome
15
Figure
6
Proposed
nmechanism
leading
to
maternal
uniparental
heterodisonmy
and
partial
trisomy
of
distal
15q.
(1)
Trisomy
rescue
event,
with
partial
loss
of
chromosome
15
and
telonmeric
translocation
of
distal
chron2osonme
15
to
chromosonie
14q.
(2)
Subsequent
translocationi
of
the
distal
15q
fragnment
from
14qter
to
the
telomeres
of
chronlosomle
4q
anld
16p.
(3)
Loss
of
the
distal
15q
fragment
fronm
the
telonmeres
might
lead
to
a
euploid
cell
line.
(4)
A
second
trisomy
rescue
event
with
loss
of
the
entire
chromosome
15
is
an
alternative
mechanism
resulting
in
a
euploid
cell
line
in
this
patient.
this,
the
patient's
karyotype
showed
partial
tri-
somy
for
distal
15q,
and
this
could
possibly
explain
why
her
mental
retardation
was
more
severe
than
usually
observed
in
PWS.
Paternal
inheritance
for
alleles
on
chromosome
15
could
only
be
shown
for
distal
chromosome
15q,
and
this,
together
with
a
maternal
origin
of
both
intact
chromosomes
15,
is
fully
compatible
with
a
paternal
origin
of
this
trans-
located
chromosomal
fragment.
The
most
likely
mechanism
explaining
these
findings
is
shown
in
fig
6.
Fertilisation
by
a
normal
male
gamete
of
a
disomic
oocyte
results
in
a
zygote
with
trisomy
15.
These
embryos
are
unviable,
unless
a
postzygotic
correction
occurs.
The
loss
of
the
paternal
chromosome
15
results
in
a
UPD
15
mat.
Trisomy
rescue
is
a
recognised
mechanism
leading
to
UPD.'7
lx
Interestingly,
whereas
the
correction
usually
involves
the
loss
of
the
entire
chromosome
15,
a
partial
loss
of
chromosome
15
occurred
in
this
patient.
The
distal
chromosome
1
5q
fragment
was
retained
and
translocated
to
other
chromosomes,
result-
ing
in
partial
trisomy
for
distal
15q.
To
our
knowledge,
this
is
the
first
report
showing
that
in
trisomy
rescue
both
UPD
and
partial
trisomy
can
occur
simultaneously.
The
distal
15q
fragment
in
this
patient
was
present
as
a
jumping
translocation
involving
three
different
recipient
partners,
chromo-
somes
14q,
4q,
and
16p.
In
addition,
a
normal
46,XX
cell
line
without
the
partial
trisomy
was
found,
an
unprecedented
finding
in
patients
with
a
jumping
translocation.3
"
This
cell
line
also
has
a
UPD
15
mat,
since
in
skin
fibroblasts,
where
approximately
50%
of
the
cells
have
a
46,XX
karyotype,
an
exclusively
maternal
methylation
pattern
was
detected.
The
results
of
the
microsatellite
analysis
are
also
fully
con-
sistent
with
this.
There
are
several
different
possible
explana-
tions
for
these
observations.
In
a
first
possible
mechanism,
translocation
of
the
distal
1
5q
fragment
to
another
chromosome
coincides
with
the
process
of
trisomy
rescue
(fig
6).
Dur-
ing
subsequent
cell
divisions,
this
fragment
is
then
translocated
to
other
chromosomes,
that
is,
a
real
jumping
process
(fig
6).
This
mechanism
has
been
proposed
before.3
The
euploid
46,XX
cell
line
could
be
the
result
of
the
loss
of
the
distal
1
5q
chromosomal
fragment
during
the
jumping
process
(fig
6,
step
3).
Alternatively,
an
independent
trisomy
rescue
event
might
have
occurred
in
a
different
cell
line
with
the
loss
of
an
entire
paternal
chromosome
15
(fig
6,
step
4)
or
after
trisomy
rescue,
the
distal
chromosome
1
5q
could
initially
remain
as
a
free
acentric
chromosome
fragment.
During
subsequent
cell
divisions
and
in
different
cells,
the
fragment
could
either
be
lost
or
translocated
to
different
chromosomes.
In
this
patient,
the
telomeric
regions
of
the
translocation
partners
appeared
cytogeneti-
cally
intact.
In
addition,
by
means
of
FISH,
interstitial
telomeric
sequences
were
shown
at
the
breakpoint
junctions.
This
would
imply
an
initial
translocation
of
the
distal
15q
fragment
to
the
telomere
of
one
chromosome.
The
pres-
ence
of
interstitial
telomeres
might
render
these
derivative
chromosomes
unstable
and
prone
to
breakage
at
this
site
and
recombina-
tion
with
other
telomeric
sequences,
as
was
suggested
before.4
The
jumping
translocation
process
would
then
not
represent
a
recurrent
reciprocal
translocation
but
rather
a
transposi-
tion
of
a
chromosomal
fragment
from
one
telo-
mere
to
another.
Loss
of
the
chromosome
398
group.bmj.com on July 13, 2011 - Published by jmg.bmj.comDownloaded from

J7umping
translocation
in
Prader-Willi
syndrome
15qter
fragment,
leading
to
a
euploid
cell
line,
would
occur
upon
chromosome
breakage
at
the
junction
site
without
a
simultaneous
recombination
with
another
telomere.
Further
experimental
evidence
to
support
this
mech-
anism
could
be
gained
from
long
term
cultures
of
clonal
cell
lines
carrying
a
jumping
translo-
cation,
and
the
finding
of
either
a
loss
of
the
fragment
or
transposition
to
the
telomeres
of
another
chromosome.
Another
proposed
mechanism
would
require
that
the
distal
chromosome
1
5q
acentric
chro-
mosome
fragment
remains
stable
during
sev-
eral
sequential
cell
divisions
before
being
lost
or
translocated
to
the
telomeres
of
different
chromosomes.
It
is
difficult
to
envisage
how
a
chromosomal
fragment
without
a
centromere
and
missing
a
telomere
at
one
end
could
be
stably
retained
during
several
cell
divisions.
Therefore,
we
favour
the
first
mechanism.
Interestingly,
besides
one
patient
with
a
breakpoint
in
chromosome
17q23,
all
seven
other
reported
patients
with
a
telomeric
trans-
location
have
a
breakpoint
in
chromosome
15ql1-13
and
have
the
PWS
phenotype."6
Involvement
of
the
same
chromosomal
region
has
led
to
the
suggestion
that
in
this
chromo-
somal
region
specific
DNA
sequences
must
be
present,
with
an
affinity
for
recombination
with
telomeres.4
6
On
the
other
hand,
in
the
two
other
patients
with
a
constitutional
jumping
translocation
investigated
so
far,
interstitial
telomeric
sequences
were
also
found,
as
in
the
present
case
(case
1
of
Park
et
al,5
case
3
of
Rossi
et
at).
The
detection
of
interstitial
telomeres
in
the
present
patient
with
a
breakpoint
in
15q24
suggests
that
the
jumping
process
could
be
related
to
the
presence
of
interstitial
telomeric
sequences
and
not
merely
to
the
chromosomal
region
involved.
Addi-
tional
studies
are
needed
and,
more
specifi-
cally,
molecular
cloning
of
the
breakpoint
region
on
1
5q24
will
be
of
particular
interest
in
addressing
this
question.
In
conclusion,
the
present
observation
is
a
further
illustration
of
trisomy
rescue
leading
to
uniparental
disomy
and
shows
the
presence
of
UPD
in
association
with
a
partial
trisomy.
A
similar
observation
has
been
made
before
in
a
patient
with
UPD16
mat
and
mosaic
trisomy
for
distal
16p.'9
For
the
first
time,
interstitial
telomere
sequences
were
also
found
in
a
constitutional
jumping
translocation
involving
a
chromosomal
region
outside
15ql
1-13.
Therefore,
we
suggest
that
the
jumping
process
is
related
to
the
presence
of
interstitial
telomeres.
We
thank
Reinhilde
Thoelen
for
expert
technical
help
and
Eric
Schoenmakers
for
the
FES
probe.
This
work
is
supported
by
a
krediet
aan
navorser,
1994,
from
the
Nationaal
Fonds
voor
Wetenschappelijk
Onderzoek
of
Belgium.
Peter
Marynen
is
a
onderzoeksdirecteur
and
Gert
Matthijs
and
Joris
Vermeesch
are
aangesteld
navorsers
of
the
Nationaal
Fonds
voor
Wetenschap-
pelijk
Onderzoek,
Belgium.
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and
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doi: 10.1136/jmg.34.5.395
1997 34: 395-399J Med Genet
K Devriendt, P Petit, G Matthijs, et al.
syndrome.
translocation of distal 15q in Prader-Willi
Trisomy 15 rescue with jumping
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