Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: Novel compound-heterozygous variants of SKIV2L gene that cause Trichohepatoenteric Syndrome (THES) 2

PROVIDER: PRJNA753967 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR15422060_1.fastq.gz	Fastqsanger.gz
	SRR15422060_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 2 of 2

Similar Datasets

Heterozygous variants in MGP lead to endoplasmic reticulum stress causing spondyloepiphyseal dysplasia

Project description:Matrix Gla protein (MGP) is a vitamin K-dependent post-translationally modified protein, highly expressed in vascular and cartilaginous tissues. It is a potent inhibitor of extracellular matrix mineralization. Biallelic loss of function variants in the MGP gene cause Keutel syndrome, an autosomal recessive disorder characterized by widespread calcification of various cartilaginous tissues and skeletal and vascular anomalies. In this study, we report four individuals from two unrelated families with two heterozygous variants in MGP, both altering the Cysteine 19 residue to phenylalanine or tyrosine. These individuals presented with a spondyloepiphyseal skeletal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. We investigated the cellular and molecular effects of one of the heterozygous deleterious variants (C19F) using both cell and genetically modified mouse models. Heterozygous ‘knock-in’ mice expressing C19F MGP recapitulated most of the skeletal anomalies observed in the affected individuals. We demonstrated that the main underlying mechanism leading to the observed skeletal dysplasia is endoplasmic reticulum stress-induced apoptosis of the growth plate chondrocytes. Our findings support that heterozygous variants in MGP altering Cys19 residue cause autosomal dominant spondyloepiphyseal dysplasia, a condition distinct from Keutel syndrome both clinically and molecularly.

2024-01-26 | PXD043374 | Pride

Homo sapiens

Project description:Novel Compound Heterozygous Variants in LTBP2 Associated with Relative Anterior Microphthalmia

| PRJNA846598 | ENA

Compound heterozygous mutations in the kinase domain of IKKα lead to immunodeficiency and immune dysregulation

Project description:IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. Absence of IKKα cause fetal encasement syndrome in human, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and cause combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were kinase dead mutants. Non-canonical NF-κB activation was abolished in stromal and immune cells while the canonical pathway was partially impaired. Reintroducing wild-type CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of bi-allelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding and suggesting IKKα's role in both NF-κB pathways.

2024-11-24 | GSE267600 | GEO

Heterozygous OAS1 Gain-of-Function Variants Cause a Polymorphic Autoinflammatory and Immunodeficiency Syndrome

Project description:Heterozygous OAS1 Gain-of-Function Variants Cause a Polymorphic Autoinflammatory and Immunodeficiency Syndrome

| PRJNA726563 | ENA

Heterozygous variants in POLR1A cause diverse human phenotypes

Project description:Heterozygous variants in POLR1A cause diverse human phenotypes

| PRJNA849583 | ENA

Project description:Novel Compound Heterozygous Variants in PCCB Gene Causing Adult-onset Propionic Acidemia Presenting with Neuropsychiatric Symptoms

| PRJNA802806 | ENA

Heterozygous variants in POLR1A cause diverse human phenotypes

Project description:Heterozygous pathogenic variants in POLR1A were identified as the cause of Acrofacial Dysostosis, Cincinnati-type in 2015. Craniofacial anomalies reminiscent of Treacher Collins syndrome were the predominant phenotype observed in the first 3 affected individuals. We have subsequently identified 17 additional individuals with 12 unique (11 novel) heterozygous variants in POLR1A and observed numerous additional phenotypes including developmental delay, infantile spasms, and structural cardiac defects. To understand the pathogenesis of this pleiotropy, we created an allelic series of POLR1A using a combination of in vivo (mouse) and in vitro models. We describe distinct spatiotemporal requirements for Polr1a during mouse embryogenesis and identify a requirement for Polr1a for survival of pre migratory and migratory neural crest cells, forebrain precursors, and the second heart field. We used CRISPR/Cas9 to recapitulate two human alleles in mouse, demonstrating pathogenicity of one and likely benign nature of the other. Our work greatly expands the phenotype of human POLR1A-related disorders, provides new evidence of reduced penetrance and variable expression of POLR1A heterozygous variants, and demonstrates a multi-faceted approach to characterize and define pathogenicity of variants.

2022-08-15 | GSE206197 | GEO

Project description:Compound heterozygous CYP1B1 gene mutations

| PRJNA715721 | ENA

Biallelic RNU12 noncoding variants cause CDAGS syndrome

Project description:Biallelic RNU12 noncoding variants cause CDAGS syndrome

| PRJNA648415 | ENA

Rare germline heterozygous missense variants of the BRCA1-Associated Protein 1 gene, BAP1, heterozygous missense variants cause a syndromic neurodevelopmental disorder

Project description:Rare germline heterozygous missense variants of the BRCA1-Associated Protein 1 gene, BAP1, heterozygous missense variants cause a syndromic neurodevelopmental disorder

| PRJNA786928 | ENA

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