Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: Mutations in spliceosomal genes PPIL1 and PRP17 cause neurodegenerative pontocerebellar hypoplasia with microcephaly

PROVIDER: PRJNA669300 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12880724_1.fastq.gz	Fastqsanger.gz
	SRR12880724_2.fastq.gz	Fastqsanger.gz
	SRR12880725_1.fastq.gz	Fastqsanger.gz
	SRR12880725_2.fastq.gz	Fastqsanger.gz
	SRR12880726_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

Project description:Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenine and guanine nucleotides. We describe a new early-onset distinct neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new potentially treatable early-onset neurodegenerative disease. An 18 chip study, that compares iPSC derived neural progenitor cells from two individuals: a patient with pontocerebellar hypoplasia and an unaffected parent. Samples are run as either non-treated, treated with Adenosine, or treated with Adenosine and AICAr. Three replicates are included for every individuals in every treatment condition.

2013-12-01 | E-GEOD-46615 | biostudies-arrayexpress

Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia

Project description:Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause Pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial Complex I and PDHc deficiency. Whole exome sequencing uncovered a known EXOSC3-mutation p.(D132A) as the underlying cause. In patient fibroblasts, >50% of the EXOSC3 protein was trapped in the cytosol. mtDNA-copy numbers in muscle were reduced to 40%, but mutations in the mtDNA and nuclear mitochondrial genes were excluded. RNA-seq of patient muscle showed highly increased mRNA-copy numbers, especially for genes encoding structural subunits of OXPHOS-complexes I, III, and IV, possibly due to reduced degradation by a dysfunctional exosome complex. This is the first case of mitochondrial dysfunction associated with an EXOSC3 mutation, which expands the phenotypic spectrum of PCH1B. We discuss the links between exosome and mitochondrial dysfunction.

2017-08-22 | GSE99715 | GEO

The ESCRT-III protein CHMP1A mediates secretion of sonic hedgehog on a novel class of extracellular vesicles

Project description:Extracellular vesicles (EVs) enable cell-to-cell communication in the nervous system essential for development and adult function. Endosomal Sorting Complex Required for Transport (ESCRT) complex proteins regulate EV formation and release. Recent work shows loss of function (LOF) mutations in, CHMP1A, which encodes one ESCRT-III member, cause autosomal recessive microcephaly with pontocerebellar hypoplasia in humans (Mochida et al., 2012). Here we show CHMP1A is required for maintenance of progenitors in human cerebral organoids and that mouse Chmp1a is required for progenitor proliferation in cortex and cerebellum and specifically for sonic hedgehog (SHH) mediated proliferation through SHH secretion. CHMP1A mutation reduces intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs), and EV release. SHH protein is present on a subset of EVs marked by a unique set of proteins we call ART-EVs. CHMP1A’s requirement in formation of ART-EVs and other EVs provides a model to elucidate EV functions in multiple brain processes.

2018-06-16 | GSE115867 | GEO

Molecular Characterization of Pontocerebellar Hypoplasia

Project description:Molecular Characterization of Pontocerebellar Hypoplasia

| PRJNA1062911 | ENA

Molecular Characterization of Pontocerebellar Hypoplasia

Project description:Molecular Characterization of Pontocerebellar Hypoplasia

| PRJNA1062912 | ENA

Pathogenic CLP1 p.R140H mutation alters mRNA processing in human motor neurons (tRNA-seq)

Project description:Pontocerebellar Hypoplasia Type 10 (PCH10) is a childhood neurodegenerative disease caused by bi-allelic p.R140H variants in CLP1, a multifunctional RNA kinase, by unknown pathophysiological mechanisms. Here, we combine novel patient data with mutation-specific in vivo and in vitro models to define motor neuron dysfunction as a penetrant, prominent feature of PCH10 and uncover a previously unrecognized mRNA misprocessing signature in motor neurons that likely contributes to pathology.

2021-11-01 | GSE183871 | GEO

Pathogenic CLP1 p.R140H mutation alters mRNA processing in human motor neurons (total RNA-seq)

2021-11-01 | GSE183870 | GEO

Pathogenic CLP1 p.R140H mutation alters mRNA processing in human motor neurons (PAC-seq)

2021-11-01 | GSE183869 | GEO

The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain

Project description:Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate RNA levels. Inherited mutations in genes encoding ubiquitous RNases are associated with human diseases, primarily affecting the nervous system. Recessive mutations in genes encoding an evolutionarily conserved RNase complex, the RNA exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b). We establish a CRISPR/Cas9-engineered Drosophila model of PCH1b to study cell-type-specific post-transcriptional regulatory functions of the nuclear RNA exosome complex within fly head tissue. Here, we report that pathogenic RNA exosome mutations alter activity of the complex, causing widespread dysregulation of brain-enriched cellular transcriptomes, including rRNA processing defects—resulting in tissue-specific, progressive neurodegenerative effects in flies. These findings provide a comprehensive understanding of RNA exosome function within a developed animal brain and underscore the critical role of post-transcriptional regulatory machinery in maintaining cellular RNA homeostasis within the brain.

2024-11-01 | GSE280166 | GEO

Homo sapiens

Project description:Biallelic mutations in the 3’ exonuclease TOE1 cause Pontocerebellar Hypoplasia Type 7 and result in snRNA processing defects

| PRJNA291458 | ENA