scholarly journals Hereditary spastic paraplegia associated with a rare endoplasmic reticulum lipid raft-associated protein 2 mutation

2020 ◽  
Vol 7 (10) ◽  
pp. 2077
Author(s):  
Sai Chandar Dudipala ◽  
Naveen Reddy Cheruku ◽  
Krishna Chaithanya Battu
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Palsy ◽  
Lipid Raft ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Recessive ◽  
Adult Population ◽  
Complex Form ◽  
Spastic Paraplegia ◽  
Childhood Onset ◽  
Exonic Deletion

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that are characterized by progressive spasticity of the lower extremities. It can present as pure form or complex form. It can be present from infancy to adulthood, but majority in adult population. Childhood onset HSP must be differentiated from common conditions like cerebral palsy, neurodegenerative disorders and metabolic disorders. Many patients with pediatric HSP are mistakenly diagnosed with cerebral palsy. In children with spastic paraplegia in whom no acquired cause identified, HSP should be considered. Here we diagnosed a 6-year-old boy with HSP who presented with progressive spastic paraplegia, intellectual disability, seizures, joint contractures and cataract. His genetic study revealed exonic deletion of endoplasmic reticulum lipid raft-associated protein gene, which is associated with complicated Autosomal recessive HSP 18 (SPG18). HSP 18 was rarely described in literature.

scholarly journals Disease Severity and Motor Impairment Correlate With Health-Related Quality of Life in AP-4-Associated Hereditary Spastic Paraplegia

2021 ◽  
Vol 7 (4) ◽  
pp. e605
Author(s):  
Catherine Jordan ◽  
Gregory Geisel ◽  
Julian E. Alecu ◽  
Bo Zhang ◽  
Mustafa Sahin ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cerebral Palsy ◽  
Hereditary Spastic Paraplegia ◽  
Motor Impairment ◽  
Health Related Quality ◽  
Spastic Paraplegia ◽  
Childhood Onset ◽  
Related Quality ◽  
Health Related

ObjectiveAP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a childhood-onset neurogenetic disease and mimic of cerebral palsy. Data on health-related quality of life (HRQoL) are lacking. To establish a metric for HRQoL and caregiver priorities, we used the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire to assess HRQoL in correlation with disease severity in 64 patients with AP-4-HSP.MethodsA cross-sectional analysis of caregiver-reported HRQoL was performed using the CPCHILD questionnaire in combination with a detailed clinical characterization.ResultsHRQoL was impaired in all domains in patients with AP-4-HSP (mean score: 59.6 ± 12.6 [SD]), with no significant difference between the 4 subtypes. Age, as a surrogate for disease duration, and Spastic Paraplegia Rating Scale scores, as an indicator for corticospinal tract dysfunction and motor impairment, correlated with lower CPCHILD scores (Pearson r = −0.31, p = 0.01 and r = −0.52, p < 0.0001, respectively). Patients with tetraplegia showed lower CPCHILD scores compared with individuals with diplegia or no spasticity. Wheelchair dependence reduced HRQoL in all domains. The presence of seizures, including medically refractory epilepsy, was not associated with lower CPCHILD scores. Standardized assessment of caregiver priorities identified several areas of high importance to HRQoL.ConclusionsWe show that the CPCHILD questionnaire, developed for use in children with cerebral palsy, can be used to assess HRQoL in patients with childhood-onset complex hereditary spastic paraplegia. HRQoL is reduced in patients with AP-4-HSP and correlates with the degree of motor impairment. These results provide a framework for medical decision making and a baseline for the future development of treatment guidelines and interventional trials.

scholarly journals Novel Mutations in Endoplasmic Reticulum Lipid Raft-associated Protein 2 Gene Cause Pure Hereditary Spastic Paraplegia Type 18

2016 ◽  
Vol 129 (22) ◽  
pp. 2759-2761 ◽  
Author(s):  
Wo-Tu Tian ◽  
Jun-Yi Shen ◽  
Xiao-Li Liu ◽  
Tian Wang ◽  
Xing-Hua Luan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Raft ◽  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Novel Mutations

scholarly journals Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Belgin Yalçın ◽  
Lu Zhao ◽  
Martin Stofanko ◽  
Niamh C O'Sullivan ◽  
Zi Han Kang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hereditary Spastic Paraplegia ◽  
Membrane Curvature ◽  
Degenerative Disease ◽  
Ultrastructural Analysis ◽  
Motor Axons ◽  
Spastic Paraplegia ◽  
Partial Loss ◽  
And Function ◽  
Tubular Endoplasmic Reticulum

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

scholarly journals Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Matias Wagner ◽  
Daniel P. S. Osborn ◽  
Ina Gehweiler ◽  
Maike Nagel ◽  
Ulrike Ulmer ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hereditary Spastic Paraplegia ◽  
Degradation Pathway ◽  
Therapeutic Interventions ◽  
Spastic Paraplegia ◽  
Ubiquitin E3 Ligase ◽  
Wide Range ◽  
Inositol 1,4,5 Trisphosphate ◽  
Cerebellar Ataxias ◽  
Trisphosphate Receptor

Abstract Alterations of Ca2+ homeostasis have been implicated in a wide range of neurodegenerative diseases. Ca2+ efflux from the endoplasmic reticulum into the cytoplasm is controlled by binding of inositol 1,4,5-trisphosphate to its receptor. Activated inositol 1,4,5-trisphosphate receptors are then rapidly degraded by the endoplasmic reticulum-associated degradation pathway. Mutations in genes encoding the neuronal isoform of the inositol 1,4,5-trisphosphate receptor (ITPR1) and genes involved in inositol 1,4,5-trisphosphate receptor degradation (ERLIN1, ERLIN2) are known to cause hereditary spastic paraplegia (HSP) and cerebellar ataxia. We provide evidence that mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts, mutant SH-SY5Y cells and by gene knockdown in zebrafish. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias and cerebellar ataxias and thus prioritize this pathway for therapeutic interventions.

Sign in / Sign up

Export Citation Format

Share Document