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Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome.
[proteus syndrome]
Cowden
syndrome
(
CS
)
,
Bannayan-
Riley
-
Ruvalcaba
syndrome
(
BRRS
)
and
proteus
syndrome
are
disorders
known
as
PTEN
hamartoma
tumour
syndrome
(
PHTS
)
,
that
can
show
remarkable
clinical
overlap
and
are
all
caused
by
germline
PTEN
mutations
.
We
here
present
two
families
,
one
affected
by
CS
and
the
other
affected
by
BRRS
,
both
carriers
of
specific
pathogenetic
missense
mutation
in
exon
5
of
PTEN
gene
,
within
the
catalitic
domain
.
Both
PHTS
families
exhibited
extremely
variable
phenotypes
,
showing
inter-
and
intra-
familial
variability
.
One
of
the
two
characterised
mutations
,
the
c
.
320
A-
 
>
 
T
;
p
.
107
Asp-
 
>
 
Val
,
identified
in
the
CS
family
,
was
not
previously
described
in
the
literature
.
Furthermore
,
the
BRRS
family
,
carrier
of
the
c
.
406
Â
T
-
 
>
 
C
;
p
.
136
Cys-
 
>
 
Arg
mutation
,
shows
a
substantial
alteration
of
PTEN
protein
expression
that
well
correlates
with
intra-familial
phenotypic
variability
.
Finally
,
we
describe
an
apparently
sporadic
case
of
an
80
-
year
-old
man
,
with
a
very
low
level
of
PTEN
mRNA
and
protein
expression
,
both
in
healthy
and
tumour
colon
mucosa
,
associated
with
a
very
atypical
phenotype
.
He
developed
a
metastatic
colorectal
carcinoma
,
macrocephaly
and
pheochromocytoma
.
According
to
literature
data
,
our
observations
confirm
that
PTEN
mutations
of
catalytic
domain
can
cause
different
syndromes
.
We
suggest
that
PTEN
expression
could
represent
one
of
the
mechanisms
involved
in
the
remarkable
heterogeneity
of
the
clinical
PHTS
manifestations
within
affected
families
.
Furthermore
,
constitutive
strong
decrease
of
PTEN
expression
in
colon
normal
mucosa
could
be
associated
with
late
onset
of
colorectal
cancer
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated