2,875 results match your criteria: "Hereditary Spastic Paraplegia"

Hereditary spastic paraplegias: When to expect bladder dysfunction a genetic and urodynamic study.

Eur J Neurol

January 2025

Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), INSERM, CNRS, Assistance Publique-Hôpitaux de Paris (APHP), University Hospital Pitié-Salpêtrière, Paris, France.

Background: The aim of this study was to characterize hereditary spastic paraplegias (HSP) patients' urodynamic profiles and development of bladder symptoms.

Methods: This is a multicentric retrospective study which included patients presenting with bladder disorders. We reviewed medical and urodynamic records in individuals with HSP and recorded age at onset of gait and bladder disorders, disability stage at the time of urodynamic assessment.

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Diagnosing hereditary spastic paraplegia (HSP) in paediatric patients can be challenging, especially when there is no positive family history. Children are often initially misdiagnosed with cerebral palsy due to the gradual progression of the disease and non-specific neuroimaging findings, despite the absence of perinatal insult. This misdiagnosis can prevent timely prenatal diagnosis, limiting the ability to make informed decisions about the pregnancy and to plan early interventions.

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Patients with Hereditary Spastic Paraplegia (HSP) report reduced quality of life (QoL) compared to the general population. Generic QoL measures do not address disease-specific aspects such as spasticity, access to specialty HSP clinics, and bladder symptoms. We designed and validated a HSP-specific QoL scale (HSPQoL), intended for use in standard clinical settings and clinical trials.

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Ovarian cancer (OV) ranks among the deadliest gynecological cancer, known for its high risk of relapse and metastasis, and a general resistance to conventional platinum-based chemotherapy. Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated.

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Kinesin-3 KIF1A (UNC-104 in C. elegans) is the major axonal transporter of synaptic vesicles and mutations in this molecular motor are linked to KIF1A-associated neurological disorders (KAND), encompassing Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis and hereditary spastic paraplegia. UNC-104 binds to lipid bilayers of synaptic vesicles via its C-terminal PH (pleckstrin homology) domain.

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Lysosomes and related precursor organelles robustly build up in swollen axons that surround amyloid plaques and disrupted axonal lysosome transport has been implicated in worsening Alzheimer's pathology. Our prior studies have revealed that loss of Adaptor protein-4 (AP-4) complex function, linked primarily to Spastic Paraplegia (HSP), leads to a similar build of lysosomes in structures we term "AP-4 dystrophies". Surprisingly, these AP-4 dystrophies were also characterized by enrichment of components of APP processing machinery, β-site cleaving enzyme 1 (BACE1) and Presenilin 2.

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Hereditary spastic paraplegias represent a rare set of monogenic disorders encompassing 79 distinct genetic variations. The principal culprit behind recessive hereditary spastic paraplegia is frequently attributed to mutations in the spastic paraplegia gene, particularly type 11, closely followed by type 15. This category is typically characterized by nonspecific clinical features, including cognitive decline, which may precede the development of progressive lower limb weakness and spasticity.

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[Successful application of preimplantation genetic testing combined with thirdgeneration sequencing for blocking hereditary spastic paraplegia].

Nan Fang Yi Ke Da Xue Xue Bao

November 2024

Department of Reproductive Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjng 210002, China.

Article Synopsis
  • A family with hereditary spastic paraplegia (HSP) due to mutations in the SPAST gene underwent third-generation sequencing (TGS) and preimplantation genetic testing (PGT) to prevent passing the condition to their children.
  • They identified a specific mutation in the SPAST gene and used advanced genetic testing during in vitro fertilization to select embryos free of the mutation.
  • The successful process resulted in the birth of a healthy baby girl, demonstrating that TGS and PGT-M are effective methods for managing hereditary diseases and ensuring the health of offspring.
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Patient-Relevant Digital-Motor Outcomes for Clinical Trials in Hereditary Spastic Paraplegia Type 7: A Multicenter PROSPAX Study.

Neurology

December 2024

Division Translational Genomics of Neurodegenerative Diseases (L.B., A.T., D.M., M.S.), Hertie-Institute for Clinical Brain Research and Center for Neurology, and German Center for Neurodegenerative Diseases (DZNE) (L.B., A.T., D.M., K.D.-J., M.S., R.S.), University of Tübingen; Section Computational Sensomotorics (J.S., W.I.), Hertie Institute for Clinical Brain Research; Centre for Integrative Neuroscience (CIN) (J.S., W.I.); Department of Neurodegenerative Diseases (C.K.), Hertie-Institute for Clinical Brain Research and Center for Neurology, University of Tübingen; Center for Neurology and Hertie Institute for Clinical Brain Research (K.D.-J., R.S.), University Hospital Tübingen, Germany; Molecular Medicine (I.R., S.S.), IRCCS Fondazione Stella Maris, Pisa, Italy; Koç University (N.A.B.), Translational Medicine Research Center, KUTTAM-NDAL, Istanbul, Turkey; Sorbonne Université (G.C.), Paris Brain Institute, INSERM, CNRS, APHP, France; Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (D.T.), University Hospital Essen, University of Duisburg-Essen, Germany; Groupe de recherche interdisciplinaire sur les maladies neuromusculaires (GRIMN) (C.G.), Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-St-Jean; Centre de recherche du Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-St-Jean (C.G.); Faculté de médecine et des sciences de la santé (C.G.), Université de Sherbrooke, Québec, Canada; Department of Neurology (B.P.C.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; and Division of Neurodegenerative Diseases (R.S.), Department of Neurology, Heidelberg University Hospital, Germany.

Article Synopsis
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Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes.

EMBO J

November 2024

Sorbonne Université, INSERM U1130, CNRS UMR8246, Neuroscience Paris Seine - Institut de Biologie Paris-Seine (NPS-IBPS), Paris, France.

The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule-severing enzymes, has emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins.

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Some subtypes of hereditary spastic paraplegia (HSP), especially with autosomal recessive inheritance (AR-HSP), have been reported rarely. In this study, we report the clinical features and molecular results of three unrelated Iranian patients with rare subtypes of HSP, including SPG76, SPG56, and SPG69; thereafter, we compare them to other reported cases. Three patients who were clinically diagnosed with HSP and born to consanguineous parents underwent molecular assessment by whole-exome sequencing (WES), followed by Sanger sequencing and co-segregation analysis.

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Article Synopsis
  • - The study investigates the retinal phenotype in two siblings with new genetic variants linked to hereditary spastic paraplegia type 56 (HSP 56), which resemble type 2 macular telangiectasis (MacTel).
  • - Five family members underwent extensive ophthalmic evaluations and genetic testing, revealing that the affected siblings exhibited specific retinal anomalies, including loss of retinal transparency and abnormal pigment distribution.
  • - The findings suggest a potential connection between the observed retinal issues and the genetic variants, indicating a shared pathway in the development of both MacTel and the hereditary condition.
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Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines.

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Article Synopsis
  • Pathological mutations in the Trk-fused gene (TFG) are linked to neurodegenerative diseases, particularly hereditary spastic paraplegia (HSP), causing lower limb issues.* -
  • Researchers used X-ray crystallography and cryo-electron microscopy to reveal how TFG forms octameric ring complexes, crucial for its function.* -
  • Mutations from HSP patients disrupt the stability of these complexes, leading to neurodegenerative effects, but different mutations have varying impacts, indicating multiple mechanisms of disease progression.*
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Article Synopsis
  • Corticospinal motor neurons (CSMNs), primarily found in the primary motor cortex, are crucial for controlling voluntary movement and are affected in several neurodegenerative diseases.
  • The FEZF2-CTIP2 genetic pathway is key to CSMN development, and the creation of a fluorescent reporter system (FEZF2:eGFP) allows for the identification of living CSMNs and their structures in lab settings.
  • This new labeling tool enhances research capabilities, providing better insights into CSMN vulnerability and related neurological disorders.
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Article Synopsis
  • Inherited motor neuron diseases (MND) like hereditary spastic paraplegias (HSP) involve the death or dysfunction of nerve cells that control muscle activity, but genetic variants may also affect other supportive cells.
  • Researchers used a rat model with a specific TFG mutation that mimics human HSP symptoms, such as motor deficits and spasticity, to investigate the source of axonopathy in the corticospinal tract.
  • Results showed that introducing the normal TFG gene into specific neurons significantly improved motor function, while targeting supportive glial cells did not yield similar benefits, highlighting the importance of neuron-focused therapies for TFG-related HSP.
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Hereditary spastic paraplegias (HSPs) are a diverse set of neurological disorders characterized by progressive spasticity and weakness in the lower limbs caused by damage to the axons of the corticospinal tract. More than 88 genetic mutations have been associated with HSP, yet the mechanisms underlying these disorders are not well understood. We replicated the pathophysiology of one form of HSP known as spastic paraplegia 15 (SPG15) in zebrafish.

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Introduction: Hypomyelinating leukodystrophies are a group of genetic disorders, characterised by severe permanent myelin deficiency. Their clinical features include developmental delay with or without neuroregression, nystagmus, central hypotonia, progressing to spasticity and ataxia. encodes the HSP60 chaperonin protein, mediating ATP-dependent folding of imported proteins in the mitochondrial matrix.

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A Homoplasmic MT-TV Mutation Associated with Mitochondrial Inheritance of Hereditary Spastic Paraplegia.

Mov Disord

October 2024

Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China.

Background: Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb weakness and spasticity, with unknown genetic cause in many cases.

Objectives: To identify novel genetic causes of HSP.

Methods: Phenotypic characterization, genetic screening, transcriptome sequencing, and peroneal nerve biopsy were conducted in a Chinese HSP family.

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Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells.

J Vis Exp

October 2024

Department of Pathology, Cedars-Sinai Medical Center; Department of Biomedical Science Education, College of Medicine, Charles R. Drew University of Medicine and Science;

Endoplasmic reticulum (ER)-mitochondria contact sites play a critical role in cell health and homeostasis, such as the regulation of Ca and lipid homeostasis, mitochondrial dynamics, autophagosome and mitophagosome biogenesis, and apoptosis. Failure to maintain normal ER-mitochondrial coupling is implicated in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and hereditary spastic paraplegia. It is of considerable significance to explore how the dysregulation of ER-mitochondrial contacts could lead to cell death and whether repairing these contacts to the normal level could ameliorate neurodegenerative conditions.

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Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome.

Genes (Basel)

October 2024

Associazione "La Nostra Famiglia", IRCCS "E. Medea", Scientific Hospital for Neurorehabilitation, Unit for Severe Disabilities in Developmental Age and Young Adults, Developmental Neurology and Neurorehabilitation, 72100 Brindisi, Italy.

Background: Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction.

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Introduction: Balance and gait impairments are common in people with hereditary spastic paraplegia (HSP) and often result in falls. Measures that identify patients at risk of falling are clinically relevant, but relatively unexplored in HSP. Here, we evaluated the potential of different balance and gait constructs to (1) identify differences between healthy controls and people with HSP and (2) discriminate between fallers and non-fallers with HSP.

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