2,187 results match your criteria Hereditary Spastic Paraplegia

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.

Brain 2021 May 10. Epub 2021 May 10.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Read More

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Spastic paraplegia preceding -related familial Alzheimer's disease.

Alzheimers Dement (Amst) 2021 2;13(1):e12186. Epub 2021 May 2.

Neurogenetics Unit 1st Department of Neurology Eginition Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece.

Introduction: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 () related familial Alzheimer's disease (AD).

Methods: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where mutation was identified, brain biopsy was performed. Read More

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Mutation-Related Disorders: Clinical and Genetic Features.

Front Pediatr 2021 21;9:657256. Epub 2021 Apr 21.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

encodes an α1 isoform of Na/K-ATPase, which is expressed abundantly in kidneys and central nervous system. variants may cause Na/K-ATPase loss of function and lead to a wide spectrum of phenotypes. This study aims to summarize the clinical and genetic features of mutation-related disorders and explore the potential correlations between phenotypes and genotypes. Read More

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Evidence of mosaicism in SPAST variant carriers in four French families.

Eur J Hum Genet 2021 May 6. Epub 2021 May 6.

Sorbonne Université, AP-HP, GH Pitié-Salpêtrière, Département de génétique, Paris, France.

Hereditary spastic paraplegias (HSP) are heterogeneous disorders, with more than 70 causative genes. Variants in SPAST are the most frequent genetic etiology and are responsible for spastic paraplegia type 4 (SPG4). Age at onset can vary, even between patients from the same family, and incomplete penetrance is described. Read More

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Mutations and Protein Interaction Landscape Reveal Key Cellular Events Perturbed in Upper Motor Neurons with HSP and PLS.

Brain Sci 2021 Apr 29;11(5). Epub 2021 Apr 29.

Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL 60611, USA.

Hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) are rare motor neuron diseases, which affect mostly the upper motor neurons (UMNs) in patients. The UMNs display early vulnerability and progressive degeneration, while other cortical neurons mostly remain functional. Identification of numerous mutations either directly linked or associated with HSP and PLS begins to reveal the genetic component of UMN diseases. Read More

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Retinal Architecture in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Insights into Disease Pathogenesis and Biomarkers.

Mov Disord 2021 Apr 23. Epub 2021 Apr 23.

Department of Clinical and Movement Neurosciences, Ataxia Centre, UCL, Queen Square Institute of Neurology, London, UK.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated.

Objective: To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers.

Methods: We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects). Read More

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A novel homozygous mutation in ATP13A2 gene causing pure hereditary spastic paraplegia.

Parkinsonism Relat Disord 2021 Mar 30;86:58-60. Epub 2021 Mar 30.

Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China. Electronic address:

SPG78 is a subtype of hereditary spastic paraplegia(HSP) caused by ATP13A2 gene mutations. SPG78 was reported as complicated HSP in several cases, but was never associated with pure HSP. Here we report the first Chinese patient carrying a novel homozygous nonsense mutation in ATP13A2 presenting with pure HSP. Read More

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Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.

BMC Gastroenterol 2021 Apr 13;21(1):163. Epub 2021 Apr 13.

The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.

Background: Deficiency of oxysterol 7α-hydroxylase, encoded by CYP7B1, is associated with fatal infantile progressive intrahepatic cholestasis and hereditary spastic paraplegia type 5. Most reported patients with CYP7B1 mutations presenting with liver disease in infancy have died of liver failure. However, it was recently reported that two patients treated with chenodeoxycholic acid survived. Read More

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Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.

Hum Mutat 2021 Apr 13. Epub 2021 Apr 13.

Oxford Centre for Genomic Medicine, Oxford, UK.

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. Read More

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The History of Gene Hunting in Hereditary Spinocerebellar Degeneration: Lessons From the Past and Future Perspectives.

Front Genet 2021 23;12:638730. Epub 2021 Mar 23.

Institut du Cerveau, INSERM U1127, CNRS UMR7225, Sorbonne Université, Paris, France.

Hereditary spinocerebellar degeneration (SCD) encompasses an expanding list of rare diseases with a broad clinical and genetic heterogeneity, complicating their diagnosis and management in daily clinical practice. Correct diagnosis is a pillar for precision medicine, a branch of medicine that promises to flourish with the progressive improvements in studying the human genome. Discovering the genes causing novel Mendelian phenotypes contributes to precision medicine by diagnosing subsets of patients with previously undiagnosed conditions, guiding the management of these patients and their families, and enabling the discovery of more causes of Mendelian diseases. Read More

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Genotype-phenotype correlations of stalk domain variants.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Apr 8:1-10. Epub 2021 Apr 8.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands.

The kinesin family member 5A () motor domain variants are typically associated with hereditary spastic paraplegia (HSP) or Charcot-Marie-Tooth 2 (), while tail variants predispose to amyotrophic lateral sclerosis (ALS) and neonatal intractable myoclonus. Variants within the stalk domain of are relatively rare. We describe a family of three patients with a complex HSP phenotype and a likely pathogenic stalk variant. Read More

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Association of an insertion mutation in PRRT2 with hereditary spastic paraplegia accompanied by polyneuropathy.

J Clin Lab Anal 2021 Apr 7:e23772. Epub 2021 Apr 7.

Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, China.

Background: Hereditary spastic paraplegia is a rare familial hereditary neurodegenerative disease caused by multiple autosomal dominant mutations. More than 50 mutant genes have been reported to be associated with this disease.

Methods: In this study, we have reported a rare insertion mutation site in PRRT2 that caused a familial disorder of hereditary spastic paraplegia accompanied by polyneuropathy. Read More

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Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia.

Ann Clin Transl Neurol 2021 May 5;8(5):1122-1131. Epub 2021 Apr 5.

Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Tübingen, Germany.

Objective: Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors.

Methods: The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Read More

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Recent advances in understanding hereditary spastic paraplegias and emerging therapies.

Fac Rev 2021 10;10:27. Epub 2021 Mar 10.

Paris Brain Institute (ICM), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.

Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Read More

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HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.

Acta Neurol Belg 2021 Apr 3. Epub 2021 Apr 3.

Department of Pediatric Neurology, Umraniye Training and Research Hospital, Istanbul, Turkey.

Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of conditions that are characterized by lower limb spasticity and weakness. Considering the clinical overlap between metabolic causes, genetic diseases, and autosomal recessive HSP, differentiation between these types can be difficult based solely on their clinical characteristics. This study aimed to investigate the genetic etiology of patients with clinically suspected HSP. Read More

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Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery.

Alan Mackay-Sim

Brain Sci 2021 Mar 22;11(3). Epub 2021 Mar 22.

Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Read More

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Refining Genotypes and Phenotypes in -Related Neurological Disorders.

Int J Mol Sci 2021 Mar 10;22(6). Epub 2021 Mar 10.

Division of Paediatric Epileptology, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Pathogenic variants in , encoding for the voltage-gated potassium channel K1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. Read More

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Balance rehabilitation with a virtual reality protocol for patients with hereditary spastic paraplegia: Protocol for a clinical trial.

PLoS One 2021 1;16(4):e0249095. Epub 2021 Apr 1.

UTP- Universidade Tuiuti do Paraná, Curitiba, Paraná, Brazil.

Background: Neurodegenerative diseases are sporadic hereditary conditions characterized by progressive dysfunction of the nervous system. Among the symptoms, vestibulopathy is one of the causes of discomfort and a decrease in quality of life. Hereditary spastic paraplegia is a heterogeneous group of hereditary degenerative diseases involving the disorder of a single gene and is characterized by the progressive retrograde degeneration of fibers in the spinal cord. Read More

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Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study.

Neurologia 2021 Mar 25. Epub 2021 Mar 25.

Servicio de Neurología, Hospital Universitario de Albacete, Albacete, España.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019.

Patients And Methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Read More

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Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: a phenotype study in an Irish cohort.

J Neurol 2021 Mar 27. Epub 2021 Mar 27.

National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24, Ireland.

Background: Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype.

Methods: Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with SPG7 attending two academic neurology units in Dublin, including the National Ataxia Clinic. Read More

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Monitoring Axonal Degeneration in Human Pluripotent Stem Cell Models of Hereditary Spastic Paraplegias.

Methods Mol Biol 2021 Mar 27. Epub 2021 Mar 27.

Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL, USA.

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegias (HSPs). HSPs are a large heterogeneous group of neurodegenerative diseases characterized by axonopathy involving the long corticospinal tract. How axons of these cortical projection neurons specifically degenerate in HSPs remains largely unclear partially due to the lack of human models to monitor the dynamic process of axonal degeneration. Read More

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Description of clinical features and genetic analysis of one ultra-rare (SPG64) and two common forms (SPG5A and SPG15) of hereditary spastic paraplegia families.

J Neurogenet 2021 Mar 26:1-11. Epub 2021 Mar 26.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder, characterized by lower-limb spasticity and weakness. To date, more than 82 loci/genes (SPG1-SPG82) have been identified that contribute to the cause of HSP. Despite the use of next-generation sequencing-based methods, genetic-analysis has failed in the finding of causative genes in more than 50% of HSP patients, indicating a more significant heterogeneity and absence of a given phenotype-genotype correlation. Read More

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Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.

J Hum Genet 2021 Mar 25. Epub 2021 Mar 25.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

In recent years, the tropomyosin-receptor kinase fused gene (TFG) has been linked to diverse hereditary neurodegenerative disorders, including a very rare complex hereditary spastic paraplegia, named spastic paraplegia type 57 (SPG57). Until now, four pathogenic homozygous variants of the TFG gene have been reported associated with SPG57. Two consanguineous Iranian families (1 and 2), the first one with two affected members and the second one with one, all with an early-onset progressive muscle weakness, spasticity, and several neurological symptoms were examined via the whole-exome sequencing. Read More

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[AP4-assocated hereditary spastic paraplegias].

Zh Nevrol Psikhiatr Im S S Korsakova 2021 ;121(2):71-78

Research Centre for Medical Genetics, Moscow, Russia.

Objective: In the course of studies of spastic paraplegias in Russian patients to detect AP4-associated forms, estimate their proportion in the total SPG group and analyze clinical and molecular characteristics.

Material And Methods: Five families of Russian ethnicity: four with SPG47, one with SPG51 (4 girls and a boy aged 2.5-9 years) were studied. Read More

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Muscle Characteristics in Pediatric Hereditary Spastic Paraplegia vs. Bilateral Spastic Cerebral Palsy: An Exploratory Study.

Front Neurol 2021 26;12:635032. Epub 2021 Feb 26.

KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium.

Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Read More

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February 2021

AAV-Mediated Gene Therapy for Glycosphingolipid Biosynthesis Deficiencies.

Trends Mol Med 2021 Mar 10. Epub 2021 Mar 10.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address:

De novo glycosphingolipid (GSL) biosynthesis defects cause severe neurological diseases, including hereditary sensory and autonomic neuropathy type 1A (HSAN1A), GM3 synthase deficiency, and hereditary spastic paraplegia type 26 (HSPG26), each lacking effective treatment. Recombinant adeno-associated virus (AAV)-mediated gene therapy has emerged as a powerful treatment for monogenic diseases and might be particularly suitable for these neurological conditions. Read More

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GCH1 mutations in hereditary spastic paraplegia.

Clin Genet 2021 Mar 13. Epub 2021 Mar 13.

Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson's disease (PD) and tetrahydrobiopterin (BH )-deficient hyperphenylalaninemia B. Recently, GCH1 mutations have been reported in five patients with hereditary spastic paraplegia (HSP). Here, we analyzed a total of 400 HSP patients (291 families) from different centers across Canada by whole exome sequencing (WES). Read More

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Coexistence of Hereditary Spastic Paraplegia Type 4 and Narcolepsy: A Case Report.

Case Rep Neurol 2021 Jan-Apr;13(1):84-91. Epub 2021 Feb 15.

Department of Internal Medicine, National Hospital Organization Niigata National Hospital, Kashiwazaki, Japan.

Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by the mutations in the gene, which encodes a microtubule-severing protein named spastin. Spastin regulates the number and mobility of microtubules and is essential for axonal outgrowth and neuronal morphogenesis. Herein, we report a patient with SPG4 harboring a novel donor splice site mutation in the gene (c. Read More

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February 2021

Application of a Clinical Workflow May Lead to Increased Diagnostic Precision in Hereditary Spastic Paraplegias and Cerebellar Ataxias: A Single Center Experience.

Brain Sci 2021 Feb 16;11(2). Epub 2021 Feb 16.

UOC Neurologia, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy.

The molecular characterization of Hereditary Spastic Paraplegias (HSP) and inherited cerebellar ataxias (CA) is challenged by their clinical and molecular heterogeneity. The recent application of Next Generation Sequencing (NGS) technologies is increasing the diagnostic rate, which can be influenced by patients' selection. To assess if a clinical diagnosis of CA/HSP received in a third-level reference center might impact the molecular diagnostic yield, we retrospectively evaluated the molecular diagnostic rate reached in our center on 192 unrelated families (90 HSP and 102 CA) (i) before NGS and (ii) with the use of NGS gene panels. Read More

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February 2021

Paroxysmal, exercise-induced, diurnally fluctuating dystonia: Expanding the phenotype of SPG8.

Parkinsonism Relat Disord 2021 Feb 17;85:26-28. Epub 2021 Feb 17.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

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February 2021