Cerebellar phenotypes in germline PTEN mutation carriers
Donatella Gambini
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorStefano Ferrero
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Pathology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorGaetano Bulfamante
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Human Pathology and Molecular Pathology Unit, TOMA Advanced Biomedical Assays, Busto Arsizio, Italy
Search for more papers by this authorLuigi Pisani
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorMassimo Corbo
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorCorresponding Author
Elisabetta Kuhn
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Pathology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence
Elisabetta Kuhn, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Email: [email protected]
Search for more papers by this authorDonatella Gambini
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorStefano Ferrero
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Pathology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorGaetano Bulfamante
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Human Pathology and Molecular Pathology Unit, TOMA Advanced Biomedical Assays, Busto Arsizio, Italy
Search for more papers by this authorLuigi Pisani
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorMassimo Corbo
Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy
Search for more papers by this authorCorresponding Author
Elisabetta Kuhn
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Pathology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence
Elisabetta Kuhn, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Email: [email protected]
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST STATEMENT
The authors declare no commercial or financial relationships that could be considered a conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
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