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Frontiers in Molecular Biosciences
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Other literature type . 2021
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Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

رؤى حول الجوانب السريرية والوراثية والمرضية للشلل النصفي التشنجي الوراثي: نظرة عامة شاملة
Authors: Liena E. O. Elsayed; Liena E. O. Elsayed; Isra Zuhair Eltazi; Ammar E. Ahmed; Giovanni Stevanin; Giovanni Stevanin; Giovanni Stevanin;

Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Abstract

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

Country
France
Keywords

FOS: Computer and information sciences, spastic paraplegia, QH301-705.5, Bioinformatics, molecular mechanisms, Hereditary spastic paraplegia, phenotype-genotype correlation, Inheritance (genetic algorithm), diagnostic gap, Gene, genetic heterogeneity, Cellular and Molecular Neuroscience, Genetic heterogeneity, Hereditary Spastic Paraplegia, Neurodegeneration with Brain Iron Accumulation, Health Sciences, Clinical phenotype, Genetics, Pathology, Molecular Biosciences, Disease, Biology (General), Genetic Basis of Neuropathies and Related Disorders, Biology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Life Sciences, clinical spectrum, allelic variants, Phenotype, Neurology, Physical medicine and rehabilitation, diagnostic yield, FOS: Biological sciences, Medicine, Gene Therapy for Spinal Muscular Atrophy, Spasticity, Neuroscience

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    65
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
65
Top 1%
Top 10%
Top 1%
Green
gold