Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Pratico AD

PROVIDER: S-EPMC10098112 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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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.

Praticò Andrea D AD Falsaperla Raffaele R Comella Mattia M Belfiore Giuseppe G Polizzi Agata A Ruggieri Martino M

Frontiers in pediatrics 20230330

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 gen ...[more]

PMID: 37063680

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Dataset Information

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

Publications

Case report: A gain-of-function of hamartin may lead to a distinct "inverse <i>TSC1</i>-hamartin" phenotype characterized by reduced cell growth.

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