Copper toxicosis in Bedlington terriers


Haywood, S.; Hall, E.J.

Veterinary Record 131(12): 272-272

1992


Copper toxicosis (CT) in the Bedlington terrier breed is an autosomal recessive disorder in which excess copper accumulates in the liver with an ensuing hepatopathy. The liver biopsy test, initially performed in young adulthood, is based on analysis of liver copper content together with a histological assessment of copper localisation and hepatocellular injury. Although largely superseded by genetic tests, it still remains today the best evaluation of phenotype.

LETTERS
Copper
toxicosis
in
Bedlington
terriers
SIR,
Copper
toxicosis
(CT)
in
the
Bedlington
terrier
breed
is
an
autosomal
recessive
disorder
in
which
excess
copper
accumulates
in
the
liver
with
an
ensuing
hepatopathy.
The
liver
biopsy
test,
ini-
tially
performed
in
young
adulthood,
is
based
on
analysis
of
liver
copper
content
together
with
a
histological
assessment
of
copper
localisation
and
hepatocellular
injury.
Although
largely
superseded
by
genetic
tests,
it
still
remains
today
the
best
evaluation
of
phenotype.
Insight
into
the
genetic
basis
of
the
disease
came
in
1997,
when
us
workers
found
a
microsatellite
marker
C04107,
with
allele
2
closely
li
nked
to
the
disease
-
causing
mutation
(Yuzbasiyan-Gurkan
and
others
1997).
A
comparable
UK
study
broadly
supported
the
US
find-
ings
(Holmes
and
others
1998).
A
caveat
issued
by
both
groups
limited
the
deriva-
tive
test
to
90
to
95
per
cent
accuracy
and
recommended
it
to
be
used
together
with
a
supportive
pedigree
to
establish
marker
linkage.
Subsequently,
we
at
the
University
of
Liverpool
confirmed
the
failure
of
the
DNA
microsatellite
marker
test
to
discriminate
between
affected
and
non
-affected
Bedlingtons
in
a
small
but
significant
percentage
of
cases,
and
have
identified
phenotypically
affected
dogs
(some
of
which
died)
in
equal
numbers
of
1-1
and
1-2
DNA
marker
categories
(Haywood
and
others
2001).
In
2002,
scientists
from
the
University
of
Utrecht
reported
the
identification
of
the
copper
toxicosis
gene
MURRI
(now
COMMDI),
in
close
proximity
to
the
mic-
rosatellite
C04107,
in
which
a
deletion
in
exon
2
of
the
COMMDI
gene
occurred
in
the
mutant
form
(van
de
Sluis
and
oth-
ers
2002).
Recently,
however,
some
CT
-
affected
Bedlington
terriers
have
been
identified
without
the
homozygous
COMMDI
deletion
in
both
the
UK,
USA
and
Australia
(Coronado
and
others
2003,
Hyun
and
others
2004),
reinforc-
ing
earlier
voiced
concerns.
Since
no
other
COMMDI
mutation
could
be
found
in
them,
we
(Haywood
and
van
de
Sluis)
have
hypothesised
that
a
second
as
yet
unknown
disease
gene
is
involved
in
Bedlington
CT
and
have
received
funding
from
the
Kennel
Club
to
try
to
identify
this
gene.
While
we
have
collected
DNA
from
many
of
these
dogs,
we
are
aware
that
in
the
UK
Bedlington
population
there
exists
dogs
that
exhibit
signs
of
liver
disease
associated
with
excess
copper
storage,
despite
having
been
identified
with
DNA
marker
as
categories
1-1
or
1-2.
It
is
of
the
utmost
importance
that
these
dogs
are
identified,
particularly
as
animals
exhibiting
DNA
marker
2-
2
have
been
largely
removed
from
the
breeding
pool,
which
has
left
a
sense
of
complacency
among
breeders.
In
a
rela-
tively
small
breeding
population,
such
as
Bedlington
terriers,
the
impact
in
time
of
an
unsuspected
carrier
of
an
unrec-
ognised
second
mutant
copper
gene
could
be
devastating,
and
the
undeniable
progress
made
over
the
years
in
eliminat-
ing
COMMDI
from
the
gene
pool
halted.
Identification
of
the
second
gene
could
also
help
the
canine
population
at
large,
as
several
other
breeds,
including
West
Highland
white
terriers,
Skye
terriers,
dobermanns,
dalmatians
and
keeshonds,
have
been
identified
with
copper
-asso-
ciated
liver
disease,
which
preliminary
screenings
have
shown
not
to
be
associ-
ated
with
COMMDI
deletion.
It
could
be
that
a
second
gene
is
responsible.
The
purpose
of
this
letter
is
to
inform
colleagues
in
small
animal
practice
as
to
the
current
situation
with
regard
to
Bedlington
terrier
CT,
and
to
alert
them
to
Bedlington
terriers
with
signs
of
liver
disease
irrespective
of
their
DNA
marker
status.
I
would
like
very
much
to
be
informed
about
these
dogs.
Also,
I
would
like
brought
to
my
attention
those
Bedlingtons
that
might
be
undergoing
a
routine
blood
test
in
which
the
parameters
indicate
a
possible
hepatopathy.
I
would
be
willing
to
offer
a
free
liver
biopsy
test
to
the
dogs
of
compliant
owners.
Susan
Haywood,
Department
of
Veterinary
Pathology,
Faculty
of
Veterinary
Science,
University
of
Liverpool,
Liverpool
L69
7Z]
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The
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November
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2006
687