Acute Gaucher Disease-Like Condition in an Indian Infant with a Novel Biallelic Mutation in the Prosaposin Gene

Devi, Akella Radha Rama; Kadali, Srilatha; Radhika, Ananthaneni; Singh, Vineeta; Kumar, Manjeet; Reddy, Gummadi Maheshwar; Naushad, Shaik Mohammad

doi:10.1055/s-0038-1675372

Cited by 8 publications

(4 citation statements)

References 29 publications

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“…2d,f,g). Given the screen phenotypes of PSAP, which were unexpected based on its known functions, and the association of PSAP variants not only with lysosomal storage disorders [60][61][62] but also Parkinson's Disease 63 , we decided to further investigate the underlying mechanisms of PSAP in neuronal redox regulation.…”

Section: Loss Of Prosaposin Increases Ros and Lipid Peroxidation Leve...mentioning

confidence: 99%

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

et al. 2021

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Single-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells. Here, we present the first genomewide CRISPR interference and CRISPR activation screens in human neurons. We uncover pathways controlling neuronal response to chronic oxidative stress, which is implicated in neurodegenerative diseases. Unexpectedly, knockdown of the lysosomal protein prosaposin strongly sensitizes neurons, but not other cell types, to oxidative stress by triggering the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. We also determine transcriptomic changes in neurons following perturbation of genes linked to neurodegenerative diseases. To enable the systematic comparison of gene function across different human cell types, we establish a data commons named CRISPRbrain.

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Section: Loss Of Prosaposin Increases Ros and Lipid Peroxidation Leve...mentioning

confidence: 99%

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

et al. 2021

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show abstract

“…2d,f,g). Given the screen phenotypes of PSAP, which were unexpected based on its known functions, and the association of PSAP variants not only with lysosomal storage disorders [59][60][61] but also Parkinson's Disease 62 , we decided to further investigate the underlying mechanisms of PSAP in neuronal redox regulation.…”

Section: Loss Of Prosaposin Increases Ros and Lipid Peroxidation Levementioning

confidence: 99%

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

Tian

Abarientos

Hong

et al. 2020

Preprint

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SUMMARYSingle-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells. Here, we present the first genome-wide CRISPR interference and CRISPR activation screens in human neurons.We uncover pathways controlling neuronal response to chronic oxidative stress, which is implicated in neurodegenerative diseases. Unexpectedly, knockdown of the lysosomal protein prosaposin strongly sensitizes neurons, but not other cell types, to oxidative stress by triggering the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. We also determine transcriptomic changes in neurons following perturbation of genes linked to neurodegenerative diseases. To enable the systematic comparison of gene function across different human cell types, we establish a data commons named CRISPRbrain.

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“…A single case of acute Gaucher Disease-Like Condition in an Indian Infant with novel biallelic variant in the Prosaposin Gene was recently reported. 53 Hence, genetic diagnosis is critical in such cases.…”

Section: Clinical Biochemical and Molecular Profile Of Common Lsds In...mentioning

confidence: 99%

Lysosomal storage disorders: from biology to the clinic with reference to India

Sheth¹,

Nair²,

Jee³

2023

The Lancet Regional Health - Southeast Asia

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Acute Gaucher Disease-Like Condition in an Indian Infant with a Novel Biallelic Mutation in the Prosaposin Gene

Cited by 8 publications

References 29 publications

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis

Lysosomal storage disorders: from biology to the clinic with reference to India

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