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Cerebellar phenotypes in germline PTEN mutation carriers.
Gambini, Donatella; Ferrero, Stefano; Bulfamante, Gaetano; Pisani, Luigi; Corbo, Massimo; Kuhn, Elisabetta.
Afiliação
  • Gambini D; Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy.
  • Ferrero S; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
  • Bulfamante G; Pathology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • Pisani L; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
  • Corbo M; Human Pathology and Molecular Pathology Unit, TOMA Advanced Biomedical Assays, Busto Arsizio, Italy.
  • Kuhn E; Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy.
Neuropathol Appl Neurobiol ; 50(2): e12970, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38504418
ABSTRACT
PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Hamartoma Múltiplo / Neoplasias Cerebelares Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Hamartoma Múltiplo / Neoplasias Cerebelares Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article