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 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