Intracranial undifferentiated malign neuroglial tumor in Smith-Lemli-Opitz syndrome: A theory of a possible predisposing factor for primary brain tumors via a case report

Aslan, Ayfer; Börcek, Alp Özgün; Pamukcuoglu, Selma; Baykaner, M. Kemali

doi:10.1007/s00381-016-3214-z

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…Mutations in human HMGCS1 have not been associated with disease, but there are 8 congenital anomalies that occur as a consequence of mutations within other enzymes of the CSP. [5][6][7][8][9][10][11]13,51 These congenital anomalies are characterized by diverse phenotypes, 7,21,[51][52][53] and mutations in the zebrafish hmgcs1 gene mimic these disorders, resulting in a multiple congenital anomaly syndrome. Therefore, zebrafish with mutations in hmgcs1 have the potential to reveal novel cellular and molecular mechanisms underlying individual phenotypes across multiple genetic disorders.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development

et al. 2019

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Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is 1 potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wild-type siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal 2 novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

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Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development

et al. 2019

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“…Here we show that cholesterol and isoprenoids regulate erythropoiesis using a zebrafish harboring mutations in the hmgcs1 gene (Vu57 allele). Mutations in human HMGCS1 have not been associated with disease, but there are 8 congenital anomalies that occur as a consequence of mutations within other enzymes of the CSP [5][6][7][8][9][10][11]13,48 . These congenital anomalies are characterized by diverse phenotypes 7,21,[48][49][50] and mutations in the zebrafish hmgcs1 gene mimics these disorders resulting in a multiple congenital anomaly syndrome.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Hernández

Castro

Reyes-Nava

et al. 2018

Preprint

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word count: 187 Number of figures and tables: 5 Number of references: 72 Key Points 1. The products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis. 2. Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor. AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is one potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wildtype siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

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“…Brain malignancy in individuals with SLOS has been reported in two cases (Oslejskova et al, ; Aslan et al, ), although biochemical or molecular confirmation for the diagnosis of SLOS was not provided in the latter reference. Both groups suggested dysregulation of the Sonic hedgehog (Shh) signaling pathway to be the potential underlying tumorigenesis mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Other reviews of brain tissues from individuals with SLOS revealed poor development of the corpus callosum, disordered arrangements of cellular layers in the cerebellum, and abnormal development of cerebral gyri (Cherstvoy et al, ; Curry et al, ). Malignant brain lesions in individuals with SLOS have been reported in two cases (Oslejskova et al, ; Aslan, Borcek, Pamukcuoglu, & Baykaner, ).…”

Section: Introductionmentioning

confidence: 99%

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Spontaneously regressing brain lesions in Smith–Lemli–Opitz syndrome

Dang

Baker²,

Warren

et al. 2017

American J of Med Genetics Pt A

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Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn error of cholesterol synthesis that affects the development of many organ systems. Malformations in the central nervous system typically involve midline structures and reflect abnormal growth and differentiation of neurons and supporting cells. Despite these defects in central nervous system development, brain tumor formation has only rarely been reported in association with SLOS. We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals' clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions.

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Intracranial undifferentiated malign neuroglial tumor in Smith-Lemli-Opitz syndrome: A theory of a possible predisposing factor for primary brain tumors via a case report

Cited by 6 publications

References 31 publications

Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development

Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Spontaneously regressing brain lesions in Smith–Lemli–Opitz syndrome

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