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Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth

Mutations of TSC1 and TSC2 genes cause classical Tuberous Sclerosis Complex (TSC), a neurocutaneous disorder characterized by a tendency to develop hamartias, hamartomas, and other tumors. We herein report on a girl, now aged 5 years, who presented a previously unreported, distinct clinical phenotyp...

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Autores principales: Praticò, Andrea D., Falsaperla, Raffaele, Comella, Mattia, Belfiore, Giuseppe, Polizzi, Agata, Ruggieri, Martino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098112/
https://www.ncbi.nlm.nih.gov/pubmed/37063680
http://dx.doi.org/10.3389/fped.2023.1101026
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author Praticò, Andrea D.
Falsaperla, Raffaele
Comella, Mattia
Belfiore, Giuseppe
Polizzi, Agata
Ruggieri, Martino
author_facet Praticò, Andrea D.
Falsaperla, Raffaele
Comella, Mattia
Belfiore, Giuseppe
Polizzi, Agata
Ruggieri, Martino
author_sort Praticò, Andrea D.
collection PubMed
description Mutations of TSC1 and TSC2 genes cause classical Tuberous Sclerosis Complex (TSC), a neurocutaneous disorder characterized by a tendency to develop hamartias, hamartomas, and other tumors. We herein report on a girl, now aged 5 years, who presented a previously unreported, distinct clinical phenotype consisting of primary microcephaly (head circumference = 40 cm, −5.6 standard deviations), brain anomalies including hypoplasia of the corpus callosum (with a residual draft of the genu), simplified parieto-temporal gyral pattern, colpocephaly with ectasia of the temporal ventricular horns, intellectual disability, and a general pattern of reduced growth (with weight and height < 3rd centiles). No classical features of TSC were recorded; the girl harbored a novel missense variant in TSC1 (c.611G > A). We hypothesize that her clinical phenotype could be related to a “gain-of-function” of the TSC1 protein product hamartin, causing an increase in the effects of the protein on inhibition of its intracellular targets (i.e., mTORC or RAC1 pathways), resulting in a distinct “inverse TSC1-hamartin” phenotype characterized by reduced growth of cells instead of the more classical predisposition to increased cell growth.
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spelling pubmed-100981122023-04-14 Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth Praticò, Andrea D. Falsaperla, Raffaele Comella, Mattia Belfiore, Giuseppe Polizzi, Agata Ruggieri, Martino Front Pediatr Pediatrics Mutations of TSC1 and TSC2 genes cause classical Tuberous Sclerosis Complex (TSC), a neurocutaneous disorder characterized by a tendency to develop hamartias, hamartomas, and other tumors. We herein report on a girl, now aged 5 years, who presented a previously unreported, distinct clinical phenotype consisting of primary microcephaly (head circumference = 40 cm, −5.6 standard deviations), brain anomalies including hypoplasia of the corpus callosum (with a residual draft of the genu), simplified parieto-temporal gyral pattern, colpocephaly with ectasia of the temporal ventricular horns, intellectual disability, and a general pattern of reduced growth (with weight and height < 3rd centiles). No classical features of TSC were recorded; the girl harbored a novel missense variant in TSC1 (c.611G > A). We hypothesize that her clinical phenotype could be related to a “gain-of-function” of the TSC1 protein product hamartin, causing an increase in the effects of the protein on inhibition of its intracellular targets (i.e., mTORC or RAC1 pathways), resulting in a distinct “inverse TSC1-hamartin” phenotype characterized by reduced growth of cells instead of the more classical predisposition to increased cell growth. Frontiers Media S.A. 2023-03-30 /pmc/articles/PMC10098112/ /pubmed/37063680 http://dx.doi.org/10.3389/fped.2023.1101026 Text en © 2023 Praticò, Falsaperla, Comella, Belfiore, Polizzi and Ruggieri. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Praticò, Andrea D.
Falsaperla, Raffaele
Comella, Mattia
Belfiore, Giuseppe
Polizzi, Agata
Ruggieri, Martino
Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title_full Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title_fullStr Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title_full_unstemmed Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title_short Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth
title_sort case report: a gain-of-function of hamartin may lead to a distinct “inverse tsc1-hamartin” phenotype characterized by reduced cell growth
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098112/
https://www.ncbi.nlm.nih.gov/pubmed/37063680
http://dx.doi.org/10.3389/fped.2023.1101026
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