Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biallelic BRF2 mutations cause syndromic immunodeficiency and change RNA polymerase III-mediated transcription

ABSTRACT: Biallelic BRF2 mutations cause syndromic immunodeficiency and change RNA polymerase III-mediated transcription

PROVIDER: PRJNA1176264 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	SRR31076294_1.fastq.gz	Fastqsanger.gz
	SRR31076294_2.fastq.gz	Fastqsanger.gz
	SRR31076295_1.fastq.gz	Fastqsanger.gz
	SRR31076295_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 11

Similar Datasets

Biallelic BRF2 mutations cause syndromic immunodeficiency and change RNA polymerase III-mediated transcription

Project description:TFIIB-related factor 2 (BRF2) crucially recruits RNA polymerase III (Pol III) to type III promoters containing a TATA box. These promoters encompass crucial components such as U6 spliceosomal RNA, tRNA processing enzyme RNase P, and selenocysteine tRNA. The results on cancer occurrence due to overexpression of BRF2 are known, but genetic disorders caused by mutations in BRF2 are still not well understood. Here, we first identified biallelic BRF2 variants exhibiting defective RNA Pol III activity to type III promoter in a familial patient presenting multiple anomalous features and primary immunodeficiency.

2024-11-06 | GSE280098 | GEO

Biallelic RNU12 noncoding variants cause CDAGS syndrome

Project description:Biallelic RNU12 noncoding variants cause CDAGS syndrome

| PRJNA648415 | ENA

A single recurrent dominant variant in ITPR3 leads to a syndromic immunodeficiency

Project description:Intracellular calcium levels are finely tuned through intricate actions of a number of channels and transporters, including those at key endocellular stores, e.g. endoplasmic reticulum (ER), lysosomes, and mitochondria. Along with the highly homologous genes Inositol 1,4,5-trisphosphate (IP3) receptor type 1 (ITPR1) and 2 (ITPR2), ITPR3 encodes the IP3 receptor (IP3R), a key player in intracellular calcium release in animals. Here we report the first cases of ITPR3 defects in man leading to a primarily dysimmune phenotype. In four unrelated patients of diverse ethnicity, and suffering from a complex immunodeficiency syndrome, we report the same de novo pathogenic variant - c.7570C>T; p.Arg2524Cys - in ITPR3. Clinically, recurrent severe infectious episodes of viral and bacterial origins, features of ectodermal dysplasia and that of Charcot-Marie-Tooth disease were paramount. The identified variant does not affect gene transcription, yet it was structurally predicted and biologically proven to disrupt proper protein folding and function in vivo. This eventually leads to defective Calcium flux in patient cells, dysregulation of mitochondrial function and a broad dysimmune phenotype characterized primarily by a profound CD4 T cell lymphopenia associated with quasi absence of naïve CD4 and CD8 cells, itself mirrored by an increase in cognate memory cells. The Calcium signaling defect was recapitulated ex vivo through the introduction of this single variant in Jurkat cells. Moreover, site-directed mutagenesis displayed the exquisite sensitivity of Arg2524 to any amino acid change. In conclusion, a single unique recurrent de novo variant in ITPR3 leads to a novel syndromic immunodeficiency.

2023-07-05 | E-MTAB-13124 | biostudies-arrayexpress

NONO mutations cause syndromic intellectual disability and inhibitory synaptic defects

Project description:Identifying causes of sporadic intellectual disability remains a considerable medical challenge. Here, we demonstrate that null mutations in the NONO gene, a member of the Drosophila Behavior Human Splicing (DBHS) protein family, are a novel cause of X-linked syndromic intellectual disability. Comparing humans to Nono-deficient mice revealed related behavioral and craniofacial anomalies, as well as global transcriptional dysregulation. Nono-deficient mice also showed deregulation of a large number of synaptic transcripts, causing a disorganization of inhibitory synapses, with impaired postsynaptic scaffolding of gephyrin. Alteration of gephyrin clustering could be rescued by over-expression of Gabra2 in NONO-compromised neurons. These findings link NONO to intellectual disability and first highlight the key role of DBHS proteins in functional organization of GABAergic synapses.

2015-09-02 | E-MTAB-2895 | biostudies-arrayexpress

NONO mutations cause syndromic intellectual disability and inhibitory synaptic defects

2015-09-02 | E-MTAB-2894 | biostudies-arrayexpress

Biallelic PAX5 mutations cause hypogammaglobulinemia,sensorimotor deficits and autism spectrum disorder

Project description:Biallelic PAX5 mutations cause hypogammaglobulinemia,sensorimotor deficits and autism spectrum disorder

| PRJNA759253 | ENA

Autosomal recessive TPPII mutations cause a new human immunodeficiency

Project description:Autosomal recessive TPPII mutations cause a new human immunodeficiency

| PRJNA269323 | ENA

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

Project description:Processing of RNA polymerase II-transcribed spliceosomal small nuclear RNAs (snRNAs) initiates with cleavage by the Integrator complex, but the factors that subsequently remove 3’ end extensions from metazoan snRNAs have remained unknown. We studied human families with a unique recessive syndromic constellation of pontocerebellar atrophy with ambiguous genitalia, uncovering biallelic inactivating mutations in TOE1, which encodes a conserved unconventional deadenylase. TOE1 demonstrated tight association with snRNA-protein (snRNP) complexes with specificity for incompletely processed pre-snRNAs containing 3’ end extensions that often included post-transcriptionally added tails. Human cells deficient for TOE1 catalytic activity showed accumulation of 3’-end extended U1, U2, U4 and U5 pre-snRNAs, and TOE1 immuno-isolated from human cells was capable of processing 3’-end extended snRNPs in vitro. The missense mutations identified in patients impaired TOE1 stability and snRNA processing in patient cells, which was associated with defects in splicing. Our findings reveal the cause of a unique brain malformation and uncover a long-sought 3’ exonuclease required for snRNA processing.

2016-12-31 | GSE71536 | GEO

A single recurrent dominant variant in ITPR3 leads to a syndromic immunodeficiency

Project description:A single recurrent dominant variant in ITPR3 leads to a syndromic immunodeficiency

| PRJEB63615 | ENA

Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.

Project description:PurposeImbalances in protein homeostasis affect human brain development, with the ubiquitin-proteasome system (UPS) and autophagy playing crucial roles in neurodevelopmental disorders (NDD). This study explores the impact of biallelic USP14 variants on neurodevelopment, focusing on its role as a key hub connecting UPS and autophagy.MethodsHere, we identified biallelic USP14 variants in 4 individuals from 3 unrelated families: 1 fetus, a newborn with a syndromic NDD and 2 siblings affected by a progressive neurological disease. Specifically, the 2 siblings from the latter family carried 2 compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330∗), whereas the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs∗24) variant, and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs∗11) variant. Functional studies were conducted using sodium dodecyl-sulfate polyacrylamide gel electrophoresis, western blotting, and mass spectrometry analyses in both patient-derived and CRISPR-Cas9-generated cells.ResultsOur investigations indicated that the USP14 variants correlated with reduced N-terminal methionine excision, along with profound alterations in proteasome, autophagy, and mitophagy activities.ConclusionBiallelic USP14 variants in NDD patients perturbed protein degradation pathways, potentially contributing to disorder etiology. Altered UPS, autophagy, and mitophagy activities underscore the intricate interplay, elucidating their significance in maintaining proper protein homeostasis during brain development.

| S-EPMC11241549 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data