Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome

@article{Thiffault2004MutationAO,
  title={Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome},
  author={Isabelle Thiffault and Charles E. Schwartz and Vazken M. Der Kaloustian and William D. Foulkes},
  journal={American Journal of Medical Genetics Part A},
  year={2004},
  volume={130A}
}
Proteus syndrome is a complex hamartomatous disorder characterized by asymmetrical gigantism, epidermal nevi, vascular malformations, hamartomas, lipomas, and hyperostosis. Since the syndrome was first described, many hypotheses have been proposed to explain its occurrence. The most plausible is Happle's somatic mosaic hypothesis, but no somatic mutations in candidate genes have been reported to be clearly involved in Proteus syndrome. However, germ‐line PTEN mutations have been reported in… 
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Methods Citations
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A mosaic activating mutation in AKT1 associated with the Proteus syndrome.
TLDR
The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder.
PTEN hamartoma tumor syndromes
TLDR
Improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway means inhibitors of this pathway are being developed as anticancer agents and could have applications for patients with PHTS, for whom no medical options currently exist.
Proteus syndrome with syringohydromyelia and arachnoid cyst
TLDR
The authors make a good review of the main clinical and genetic aspects of Proteus syndrome and classify its classification, along with Cowden and Bannayan–Zonana syndromes, as part of the spectrum of PTEN hamartoma–tumor syndrome (PHTS).
Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity
TLDR
Data provide a new demonstration of the Happle hypothesis to explain some segmental exacerbation of autosomal-dominant disorders and show that a bi-allelic inactivation of PTEN can lead to developmental anomalies instead of malignant transformation, raising the question of the limitations of the tumor suppressive function in this gene.
Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers
TLDR
Careful phenotyping gives further support for the suggestion that BRRS and CS are actually one condition, presenting variably at different ages, as in other tumour-suppressor disorders such as neurofibromatosis type 1.
PTEN Hamartoma Tumor Syndrome (PHTS)-GeneReviews-NCBI Bookshelf
TLDR
Because the most serious consequences of PHTS relate to the increased risk of breast, thyroid, endometrial, and renal cancers, the most important aspect of management of an individual with a PTEN mutation is increased cancer surveillance.
PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature
TLDR
The limited understanding of the natural history of childhood‐onset PHTS as a cancer predisposition syndrome is acknowledged and a summary of important management considerations is presented.
Cerebral cavernous malformations do not fall in the spectrum of PIK3CA-related overgrowth
TLDR
This paper reviews and attempts to conceptualise the relationships and differences among clinical presentations, genotypic and phenotypic correlations and possible coexistence of PIK3CA and CCM mutations/phenotypes in CCM lesions and presents a model reflecting the hypothetical understanding of CCM pathogenesis based on a systematic review and conceptualisation of data obtained from other studies.
Overgrowth syndromes:from classical to new.
TLDR
The aim of this review is to give a comprehensive overview of the clinical, molecular genetic and pathophysiological aspects of each of the classic and new overgrowth syndromes.
Somatic gene mutation and human disease other than cancer: an update.
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References

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TLDR
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