New genetic causes for complex hereditary spastic paraplegia

New genetic causes for complex hereditary spastic paraplegia

Author Sgobbi de Souza, Paulo Victor Autor UNIFESP Google Scholar
Bortholin, Thiago Autor UNIFESP Google Scholar
Dias, Renan Braido Autor UNIFESP Google Scholar
Troccoli Chieia, Marco Antonio Autor UNIFESP Google Scholar
Burlin, Stenio Autor UNIFESP Google Scholar
Monteiro Naylor, Fernando George Autor UNIFESP Google Scholar
Vieira de Rezende Pinto, Wladimir Bocca Autor UNIFESP Google Scholar
Bulle Oliveira, Acary Souza Autor UNIFESP Google Scholar
Abstract Introduction: Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far. We performed review of medical records from twenty-one patients from seventeen Brazilian families with complex phenotype of HSP. All cases have previously negative mutations in SPG11/KIAA1840 and SPG7 gene and were evaluated by whole-exome sequencing. An extensive description of systemic and neurological signs has been described. Results: Whole-exome sequencing was unremarkable in eight patients and established a definite genetic diagnosis in thirteen patients of twelve non-related families. Mutations were found in genes previously implicated in other neurodegenerative disorders such as Amyotrophic Lateral Sclerosis, Hereditary Neuropathy, Spastic Ataxias, Neurodegeneration with Brain Iron Accumulation, Glycogen Metabolism, Congenital Lipodystrophy and aminoacyl-tRNA synthetases disorders. Conclusions: We report thirteen new genetically-proven cases of complex HSP, expanding the clinical spectrum of presentations of HSP, providing new pathophysiological mechanisms and disclosing new potential therapeutic targets. (C) 2017 Elsevier B.V. All rights reserved.
Keywords Hereditary spastic paraplegia
Spastic ataxia
Language English
Date 2017
Published in Journal Of The Neurological Sciences. Amsterdam, v. 379, p. 283-292, 2017.
ISSN 0022-510X (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 283-292
Access rights Closed access
Type Article
Web of Science ID WOS:000407184500063

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