2,416 results match your criteria Hereditary Spastic Paraplegia


SPG11 presenting with dystonic tremor in childhood.

Parkinsonism Relat Disord 2022 May 19;99:76-78. Epub 2022 May 19.

TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, NSW, Sydney, Australia; Kids Neuroscience Centre, The Children's Hospital at Westmead, NSW, Sydney, Australia; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

This is a unique case of SPG11 mutation presenting as childhood onset dystonic tremor without weakness or spastic paraplegia. Hereditary spastic paraplegia is the most common phenotype of SPG11 mutation though there are reports of an extended phenotype of SPG11 including dopa-responsive dystonia and tremor. Read More

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CNS-associated T-lymphocytes in a mouse model of Hereditary Spastic Paraplegia type 11 (SPG11) are therapeutic targets for established immunomodulators.

Exp Neurol 2022 May 19:114119. Epub 2022 May 19.

Section of Developmental Neurobiology, Department of Neurology, University Hospital, Würzburg, 97080, Würzburg, Germany. Electronic address:

Pharmacological targeting of neuroinflammation in distinct models of genetically mediated disorders of the central nervous system (CNS) has been shown to attenuate disease outcome significantly. These include mouse models mimicking distinct subtypes of neuronal ceroid lipofuscinoses (NCL, CLN diseases) as well as hereditary spastic paraplegia type 2 (HSP/SPG2). We here show in a model of another, complicated HSP form (SPG11) that there is neuroinflammation in distinct compartments of the diseased CNS. Read More

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Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review.

Neurol Sci 2022 May 21. Epub 2022 May 21.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, 40139, Bologna, Italy.

Introduction: An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP and features of relapsing-remitting MS (RRMS). We took this opportunity to review the current literature of co-occurring MS and HSP. Read More

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Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

Eur Radiol 2022 May 20. Epub 2022 May 20.

Molecular Medicine Unit, IRCCS Fondazione Stella Maris, Pisa, Italy.

Objectives: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. Read More

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Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations.

BMC Neurol 2022 May 16;22(1):180. Epub 2022 May 16.

Department of Neuromuscular Disease, The Third Affiliated Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei, 050000, PR China.

Background: Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis. Read More

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Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia.

Front Neurol 2022 28;13:872927. Epub 2022 Apr 28.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background And Purpose: A variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs.

Methods: A total of 52 patients with clinically suspected HSPs were enrolled in this study. Read More

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The Global Burden of Motor Neuron Disease: An Analysis of the 2019 Global Burden of Disease Study.

Front Neurol 2022 21;13:864339. Epub 2022 Apr 21.

Department of Neurology, Seoul Hospital Ewha Womans University College of Medicine, Seoul, South Korea.

Up-to-date, accurate information on the disease burden of motor neuron disease (MND) is the cornerstone for evidence-based resource allocation and healthcare planning. We aimed to estimate the burden of MND globally from 1990 to 2019, as part of the Global Burden of Disease, Injuries and Risk Factor (GBD) study. Amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, pseudobulbar palsy, spinal muscular atrophy and hereditary spastic paraplegia- were included for analysis as MNDs. Read More

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Cytoskeleton saga: Its regulation in normal physiology and modulation in neurodegenerative disorders.

Eur J Pharmacol 2022 May 4;925:175001. Epub 2022 May 4.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India. Electronic address:

Cells are fundamental units of life. To ensure the maintenance of homeostasis, integrity of structural and functional counterparts is needed to be essentially balanced. The cytoskeleton plays a vital role in regulating the cellular morphology, signalling and other factors involved in pathological conditions. Read More

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Exploring Motor Neuron Diseases Using iPSC Platforms.

Stem Cells 2022 03;40(1):2-13

Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.

The degeneration of motor neurons is a pathological hallmark of motor neuron diseases (MNDs), but emerging evidence suggests that neuronal vulnerability extends well beyond this cell subtype. The ability to assess motor function in the clinic is limited to physical examination, electrophysiological measures, and tissue-based or neuroimaging techniques which lack the resolution to accurately assess neuronal dysfunction as the disease progresses. Spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS) are all MNDs with devastating clinical outcomes that contribute significantly to disease burden as patients are no longer able to carry out normal activities of daily living. Read More

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Novel insights into the genetic profile of hereditary spastic paraplegia in India.

J Neurogenet 2022 May 2:1-11. Epub 2022 May 2.

Departments of Neurology and Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Read More

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Genetic, structural and clinical analysis of spastic paraplegia 4.

Parkinsonism Relat Disord 2022 Apr 16;98:62-69. Epub 2022 Apr 16.

The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada. Electronic address:

Introduction: Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). We aimed to study genetic and clinical characteristics of SPG4 across Canada.

Methods: The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). Read More

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The prodromal phase of hereditary spastic paraplegia type 4: the preSPG4 cohort study.

Brain 2022 Apr 26. Epub 2022 Apr 26.

Center for Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.

This cohort study aims to characterize the prodromal phase of hereditary spastic paraplegia type 4 (SPG4) by biomarkers and clinical signs and symptoms that develop before manifest gait abnormalities. Fifty-six first-degree relatives at risk to develop SPG4 underwent blinded genotyping and standardized phenotyping, including the Spastic Paraplegia Rating Scale (SPRS), complicating symptoms, non-motor affection, Three-Minute-Walk, and neurophysiological assessment. Automated MR image analysis was used to compare volumetric properties. Read More

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Biallelic variants in the ectonucleotidase ENTPD1 cause a complex neurodevelopmental disorder with intellectual disability, distinct white matter abnormalities, and spastic paraplegia.

Ann Neurol 2022 Apr 26. Epub 2022 Apr 26.

Department of Clinical Genetics, Erasmus MC University Medical Center, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.

Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia (HSP) is associated with over 80 genes with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (MIM# 615683). Read More

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Clinical and Genetic Features of Chinese Patients With -Related Hereditary Spastic Paraplegia Type 6.

Front Genet 2022 8;13:859688. Epub 2022 Apr 8.

Department of Neurological Diseases, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.

Mutations in the gene cause hereditary spastic paraplegia (HSP) type 6 (SPG6), which is a rare type of HSP with a frequency of less than 1% in Europe. To date, less than 30 SPG6 families and limited mutations have been reported in different ethnic regions. The clinical features are variable. Read More

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Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice.

Int J Mol Sci 2022 Apr 14;23(8). Epub 2022 Apr 14.

Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08554, USA.

Adhesion molecules regulate cell proliferation, migration, survival, neuritogenesis, synapse formation and synaptic plasticity during the nervous system's development and in the adult. Among such molecules, the neural cell adhesion molecule L1 contributes to these functions during development, and in synapse formation, synaptic plasticity and regeneration after trauma. Proteolytic cleavage of L1 by different proteases is essential for these functions. Read More

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PNPLA6/NTE, an Evolutionary Conserved Phospholipase Linked to a Group of Complex Human Diseases.

Metabolites 2022 Mar 24;12(4). Epub 2022 Mar 24.

Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR 97239, USA.

Patatin-like phospholipase domain-containing protein 6 (PNPLA6), originally called Neuropathy Target Esterase (NTE), belongs to a family of hydrolases with at least eight members in mammals. PNPLA6/NTE was first identified as a key factor in Organophosphate-induced delayed neuropathy, a degenerative syndrome that occurs after exposure to organophosphates found in pesticides and nerve agents. More recently, mutations in PNPLA6/NTE have been linked with a number of inherited diseases with diverse clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. Read More

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Age-Dependent Increase in Schmidt-Lanterman Incisures and a Cadm4-Associated Membrane Skeletal Complex in Fatty Acid 2-hydroxylase Deficient Mice: a Mouse Model of Spastic Paraplegia SPG35.

Mol Neurobiol 2022 Apr 20. Epub 2022 Apr 20.

Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Nussallee 11, 53115, Bonn, Germany.

PNS and CNS myelin contain large amounts of galactocerebroside and sulfatide with 2-hydroxylated fatty acids. The underlying hydroxylation reaction is catalyzed by fatty acid 2-hydroxylase (FA2H). Deficiency in this enzyme causes a complicated hereditary spastic paraplegia, SPG35, which is associated with leukodystrophy. Read More

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Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.

Neurogenetics 2022 Apr 9. Epub 2022 Apr 9.

Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.

The syndromic group of hereditary spastic paraplegias has a heterogeneous clinical profile and a broad differential diagnosis, including neurometabolic disorders that are potentially treatable. This group includes 5,10-methylenetetrahydrofolate reductase deficiency, cobalamin C deficiency disease, dopamine responsive dystonia, cerebrotendinous xanthomatosis, biotinidase deficiency, GLUT1 deficiency syndrome, delta-e-pyrroline-carboxylase-synthetase deficiency, hyperonithinemia-hyperammonemia-homocitrullinuria syndrome, arginase deficiency, multiple carboxylase deficiency, and X-linked adrenoleukodystrophy. This review describes these diseases in detail, highlighting the importance of early diagnosis and effective treatment aiming at preserving functionality and quality of life in these patients. Read More

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[Atypical spastic paraplegia type 4 due to p.Arg499His mutation in SPAST gene].

Zh Nevrol Psikhiatr Im S S Korsakova 2022 ;122(3):117-120

Research Centre for Medical Genetics, Moscow, Russia.

A case of spastic paraplegia type 4 (SPG4) due to p.Arg499His mutation in a child, aged 2 years 8 months, is presented. The differences of this first Russian case with the mutation and of a number of reported cases from typical SPG4 are very early onset, severe disabling spasticity and additional signs, cognitive disturbances in particular; mutations are also infrequent. Read More

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Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network.

Neurol Genet 2022 Apr 30;8(2):e664. Epub 2022 Mar 30.

Dipartimento di Neuroscienze Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, and Dipartimento di Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, UOC Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (Salvatore Rossi, V.R., Gabriella Silvestri); IRCCS Fondazione Stella Maris (A.R., M.B., R.B., I.R., A.T., R.T., F.M.S.), Calambrone, Pisa; Laboratorio di Biologia Molecolare (M.T.B.), IRCCS E. Medea, Bosisio Parini, Lecco; Dipartimento di Medicina Clinica e Sperimentale (R.B.), Università di Pisa; Unità di Malattie Neuromuscolari e Neurodegenerative (E.B., F.N., L.T.), Laboratorio di Medicina Molecolare, Dipartimento di Neuroscienze, IRCCS Ospedale Pediatrico Bambino Gesù, Rome; Dipartimento della Donna (Cristina Cereda), della Mamma, del Neonato, ASST Fatebenefratelli Sacco, Ospedale dei Bambini "V. Buzzi," Milano; Dipartimento di Scienze e Biotecnologie medico-chirurgiche (E.C., V.G., Carlo Casali), Sapienza Università di Roma; Dipartimento di Neuroscienze (Chiara Criscuolo, A.F.), Scienze Riproduttive e Odontostomatologiche, Università Federico II, Napoli; Department of Advanced Medical and Surgical Sciences (I.O., S.S., M.A.B.M.), 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania "Luigi Vanvitelli," Naples, Italy; Dipartimento di Scienze del Sistema Nervoso e del Comportamento (B.D.F.), Fondazione Istituto Neurologico C. Mondino IRCCS, Pavia; U.O. Neurologia (C.D.), IRCCS Policlinico San Donato, Milano; Unità Operativa Patologie Neuromuscolari (M.G.D.A.), IRCCS E. Medea, Bosisio Parini, Lecco; Ospedale Clinicizzato "SS Annunziata" (A.D.M.), Università di Chieti; U.O. Neuro-Oncologia (L.D.), IRCCS Mondino Foundation, Pavia; Unit of Neurology and Neurometabolic Disorders (M.T.D., Andrea Mignarri), Department of Medicine, Surgery and Neurosciences, University of Siena, Siena; IRCCS Istituto delle Scienze Neurologiche di Bologna (R.L., G.R.); Dipartimento di Scienze Biomediche e Neuromotorie (R.L.), Università di Bologna; Dipartimento di Neuroriabilitazione, IRCCS Medea, Polo di Conegliano-Pieve di Soligo (Andrea Martinuzzi), Conegliano, Treviso; Unit Malattie Neuromuscolari (Roberto Massa), Policlinico and Università di Roma Tor Vergata; Direzione Scientifica (Rossana Moroni), Fondazione Policlinico A. Gemelli IRCCS, Rome; Dipartimento di Medicina Clinica e Sperimentale (O.M.) Università di Messina; Dipartimento di Neuroscienze e Salute Mentale (L.O.), SC Neurologia 1, A.O.U Città della Salute e della Scienza di Torino; Clinica Neurologica (E.P.), Dipartimento di Neuroscienze, Azienda Ospedale Università Padova; Centro Malattie Neuromuscolari e Neurologiche Rare (A.P.), A.O. San Camillo-Forlanini, Rome; Laboratorio di Genetica Molecolare e Citogenetica (M.P.), Fondazione Istituto Neurologico C. Mondino IRCCS, Pavia; Department of Neurosciences (Silvia Romano), Mental Health and Sensory Organs, Sapienza University of Rome; Laboratorio di Neurogenetica (R.R., A.O.), Centro Europeo di Ricerca Sul Cervello, IRCCS Fondazione Santa Lucia, Rome; Dipartimento di Neurologia (Marina Scarlato), IRCCS Ospedale San Raffaele; Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, and IRCCS Azienda Ospedaliero-Universitaria di Bologna (Marco Seri), Servizio di Genetica Medica, Bologna; IRCCS E. Medea, Pieve di Soligo, Treviso; Fondazione IRCCS Istituto Neurologico Carlo Besta (Giulia Straccia), Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, Milan, Italy; Dipartimento Salute Donna e Bambino (L.U.), S.S.D. di Genetica Clinica e Biologia dello Sviluppo, Azienda ospedaliero-universitaria di Sassari; Dipartimento di Biologia (G.V.), Università degli Studi di Padova; Dipartimento di Medicina e Chirurgia (A.O.), Università di Perugia; Dipartimento di Scienze dell'Invecchiamento (Gabriella Silvestri), Neurologiche, Ortopediche e della Testa-Collo, UOC Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; and Sbarro Institute for Cancer Research and Molecular Medicine (M.A.B.M.), Center for Biotechnology, Temple University, Philadelphia, PA.

Background And Objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability. Read More

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Expansion of the mutation and phenotypic spectrum of hereditary spastic paraplegia.

Authors:
Fu Xing Juan Du

Neurol Sci 2022 Mar 28. Epub 2022 Mar 28.

Department of Neurology, Xiangya Hospital, Central South University, 87# Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.

Background: Hereditary spastic paraplegias (HSPs) are a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts, and more than 80 HSP loci have been mapped to cause HSP. In this study, we aim to perform a genetic and clinical study of ten (6 male, 4 female) sporadic Chinese HSP patients.

Methods: Next-generation sequencing (NGS) gene panels combined with multiplex ligation-dependent probe amplification assay (MLPA) analysis and the trinucleotide repeat dynamic mutation detection are available for the ten patients. Read More

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Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons.

Hum Mol Genet 2022 Mar 26. Epub 2022 Mar 26.

Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Hereditary spastic paraplegias (HSPs) comprise a large group of inherited neurologic disorders affecting the longest corticospinal axons (SPG1-86 plus others), with shared manifestations of lower extremity spasticity and gait impairment. Common autosomal dominant HSPs are caused by mutations in genes encoding the microtubule-severing ATPase spastin (SPAST; SPG4), the membrane-bound GTPase atlastin-1 (ATL1; SPG3A), and the reticulon-like, microtubule-binding protein REEP1 (REEP1; SPG31). These proteins bind one another and function in shaping the tubular endoplasmic reticulum (ER) network. Read More

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A novel UBAP1 truncated variant in a Chinese family with hereditary spastic paraplegia.

Mol Genet Genomic Med 2022 05 29;10(5):e1927. Epub 2022 Mar 29.

Department of Neurology and Research Center of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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Liver X receptor-agonist treatment rescues degeneration in a Drosophila model of hereditary spastic paraplegia.

Acta Neuropathol Commun 2022 03 28;10(1):40. Epub 2022 Mar 28.

UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.

Hereditary spastic paraplegias (HSPs) are a group of inherited, progressive neurodegenerative conditions characterised by prominent lower-limb spasticity and weakness, caused by a length-dependent degeneration of the longest corticospinal upper motor neurons. While more than 80 spastic paraplegia genes (SPGs) have been identified, many cases arise from mutations in genes encoding proteins which generate and maintain tubular endoplasmic reticulum (ER) membrane organisation. The ER-shaping proteins are essential for the health and survival of long motor neurons, however the mechanisms by which mutations in these genes cause the axonopathy observed in HSP have not been elucidated. Read More

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A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans.

Orphanet J Rare Dis 2022 03 24;17(1):133. Epub 2022 Mar 24.

E8-74 Neurology, Department of Medicine, Groote Schuur Hospital and the University of Cape Town Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Background: Genetic investigations of inherited neuromuscular disorders in Africans, have been neglected. We aimed to summarise the published data and comment on the genetic evidence related to inherited neuropathies (Charcot-Marie-Tooth disease (CMT)), hereditary spastic paraplegias (HSP) and spinal muscular atrophy (SMA) in Africans.

Methods: PubMed was searched for relevant articles and manual checking of references and review publications were performed for African-ancestry participants with relevant phenotypes and identified genetic variants. Read More

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An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15.

BMC Neurol 2022 Mar 24;22(1):115. Epub 2022 Mar 24.

Dynacure, 67400, Illkirch, France.

Background: Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. The objectives of this study were to (1) review the literature on epidemiology of HSPs; and (2) develop an epidemiological model of the prevalence of HSP, focusing on four common HSP genetic subtypes at the country and region-level. Read More

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Novel Frameshift Heterozygous Mutation in Gene Causing Spastic Paraplegia-80: Case Report With Literature Review.

Front Neurol 2022 7;13:820202. Epub 2022 Mar 7.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Hereditary spastic paraplegia (HSP) represents a group of rare inherited neurodegenerative conditions and is characterized by progressive lower limb spasticity. Ubiquitin-associated protein 1 ()-related HSP is classified as spastic paraplegia-80 (SPG80), which is an autosomal-dominant (AD) juvenile-onset neurologic disorder and mainly affects the lower limbs. We described the clinical and genetic features of two patients in the same family caused by heterozygous mutation of the gene. Read More

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European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

Eur J Neurol 2022 Jun 23;29(6):1571-1586. Epub 2022 Mar 23.

Neurology Department, Medical Faculty, University Hospital, Bern, Switzerland.

Background And Purpose: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Read More

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SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction.

Hum Mol Genet 2022 Mar 21. Epub 2022 Mar 21.

Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, Sheffield, UK.

Hereditary Spastic Paraplegia type 15 (HSP15) is a neurodegenerative condition caused by the inability to produce SPG15 protein, which leads to lysosomal swelling. However, the link between lysosomal aberrations and neuronal death is poorly explored. To uncover the functional consequences of lysosomal aberrations in disease pathogenesis, we analyze human dermal fibroblasts from HSP15 patients as well as primary cortical neurons derived from an SPG15 knockout (KO) mouse model. Read More

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