Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel Bi-Allelic Variants in RINT1 Presenting As Early-Onset Pure Hereditary Spastic Paraplegia

ABSTRACT: The hereditary spastics paraplegias (HSPs) are a group of over 80 neurogenetic disorders that share the feature of progressive lower limb spasticity. Bi-allelic loss-of-function variants in the RINT1 gene have been implicated in acute liver failure in the pediatric population, and were recently described to lead to a complex form of HSP in three children with early-onset spastic paraplegia, ataxia, optic nerve hypoplasia with significant vision impairment, dysmorphic features, and a thin corpus callosum. We read the article by Launay et al. with great interest and would like to add a fourth case due to novel biallelic RINT1 variants presenting with a largely ‘pure’ form of HSP including one missense variant and one splice site variant identifier by whole genome sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270806 | GEO | 2025/08/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hereditary Spastic Paraparesis

Project description:The goal of this project is to study differentially expressed genes in patients affected by Hereditary Spastic Paraplegia (HSP) linked to mutations of the gene encoding spastin an ubiquitously expressed protein that has recently been shown to be involved in microtubule regulation and vesicle trafficking by cell culture studies. Gene profiling was done with Affymetrix U95Av2 GeneChips using the total RNA extracted from muscle biopsies of 3 SPG4-linked HSP patients. Keywords: other

2004-04-14 | GSE1300 | GEO

Transcription profiling of human hereditary spastic paraplegia patients

2007-07-29 | E-GEOD-1300 | biostudies-arrayexpress

A patient-derived neural stem cell model for hereditary spastic paraplegia

Project description:Hereditary Spastic Paraplegia (HSP) leads to progressive gait disturbances with lower limb muscle weakness and spasticity. Mutations in SPG4 are a major cause of autosomal-dominant HSP. Spastin, the protein encoded by SPG4, is a microtubule-severing protein and is enriched in the distal axon of corticospinal motor neurons which degenerate in HSP patients. How SPG4 mutations cause axon degeneration in patients is not understood. Multipotent neural stem cells, accessible from patient olfactory mucosa biopsies, provided a new patient-derived cell models for HSP. Olfactory neurosphere-derived cells were obtained from cohorts of HSP patients with, and without, mutations in SPG4 and from healthy controls. Patient cells had extensive changes in expression of cell cycle-related genes and in genes associated with microtubule formation. Despite this, cell proliferation and metabolic functions of the patient cells were similar to controls. Cells with mutated SPG4 had significantly less spastin and acetylated tubulin but significantly more stathmin, a tubulin-depolymerising protein. These cells also significant deficits in the intracellular distribution of peroxisomes and mitochondria, compared to control cells. This model reveals that SPG4-HSP patient-derived neural stem/progenitors compensate for the cell cycle-related effects of reduced spastin levels in the nucleus, in part by large changes in gene expression, but failed to correct deficits in organelle trafficking. The results raise the question of whether these deficits arise directly from the loss of spastin or indirectly from the compensation. Patient-derived olfactory stem cells provide a new model for examining the neural consequences of human genetic mutations in their natural setting: at normal gene dosages against normal genetic backgrounds.

2012-12-20 | E-TABM-1180 | biostudies-arrayexpress

E3 ligase AMFR regulates ARL6IP1 Ubiquitination in cells

Project description:ER-resident membrane-shaping proteins with central reticulon homology domains (RHDs) have been associated with neurodegenerative disorders such as ARL6IP1 and FAM134B.Mutations in ARL6IP1 cause SPG61, a neurodegenerative disorder characterized by progressive leg spasticity (hereditary spastic paraplegia/HSP) in combination with loss of sensory and pain perception, thus reproducing typical symptoms of HSAN {Kurth, 2009 #8;Novarino, 2014 #28;Nizon, 2018 #162}.Our objetive was to analyse FAM134B-ARL6IP1 protein protein interactionS to underlying mechanisms, required for effective ER-remodelling and ER-phagy.

2023-06-19 | PXD039184 | Pride

ARL6IP1 and FAM134B forms a complex

2023-06-19 | PXD032720 | Pride

ARL6IP1 is an interacting partner of the ER-phagy receptor FAM134B

2023-06-19 | PXD032718 | Pride

GENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA

Project description:GENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA

| PRJNA313999 | ENA

KIF1A Hereditary Spastic Paraparesis

Project description:<p>The study involves a single consanguineous Palestinian family with Hereditary Spastic Paraparesis (HSP). The affected individuals suffer from spasticity of the lower limbs and abnormal gait. Using exome sequencing and homozygosity mapping, our analysis implicated the causative mutation in the motor domain of KIF1A, a gene that functions in anterograde axonal transportation.</p>

| phs000359 | dbGaP

Structural basis for membrane remodelling by the AP5:SPG11-SPG15 complex

Project description:The human spastizin (spastic paraplegia 15, SPG15) and spatacsin (spastic paraplegia 11, SPG11) complex is involved in the formation of lysosomes, and mutations in these two proteins are linked with hereditary autosomal recessive spastic paraplegia (HSP). SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes. We employed cryo-electron microscopy and in silico predictions to investigate the structural assemblies of SPG11-SPG15 and AP5:SPG11-SPG15 complex. The W-shaped SPG11-SPG15 intertwined in a head-to-head fashion, and the N-terminal region of SPG11 is required for AP5 complex interaction and assembly. The AP5 complex is in a super open conformation. Our findings reveal that the AP5:SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodelling in vitro. These studies provide key insights into the structure and function of the spastic paraplegia AP5:SPG11-SPG15 complex, which is essential for the initiation of autolysosome tubulation.

2025-03-20 | PXD054972 | Pride

Project description:SPAST variant that causes hereditary spastic paraplegia

| PRJNA623078 | ENA