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Clinical and neuroimaging features of autosomal recessive spastic paraplegia 35 (SPG35): case reports, new mutations, and brief literature review

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Abstract

Spastic paraplegia 35 (SPG35) is a recessive condition characterized by childhood onset, progressive course, complicated by dystonia, dysarthria, cognitive impairment, and epilepsy. Mutations in the FA2H gene have been described in several families, leading to the proposal of a single entity, named fatty acid hydrolase-associated neurodegeneration (FAHN). Several reports have described a polymorphic radiological picture with white matter lesions of various degrees and a distinct form of neurodegeneration with brain iron accumulation. While we reviewed the pertinent literature, we also report three new patients with SPG35, highlighting the possible absence of white matter lesions even after a long neuroimaging follow-up. Three-dimensional modeling of the mutated proteins was helpful to elucidate the role of the site of mutations and the correlation with the residual enzyme activity as determined in cultured skin fibroblasts.

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Acknowledgments

The authors thank Doctor Catherine J. Wrenn who provided expert editorial assistance. This research was supported in part by the E-RARE-3 Joint Transnational Call grant “Preparing therapies for autosomal recessive ataxias” (PREPARE) (MoH; project 3398 to FMS).

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Authors and Affiliations

  1. Pediatric Neurology Unit, Children’s Hospital A. Meyer, University of Firenze, Viale Pieraccini 24, 50139, Florence, Italy

    Francesco Mari, Beatrice Berti, Riccardo Rizzi, Elena Procopio & Renzo Guerrini

  2. Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Alessandro Romano

  3. IRCCS Stella Maris, via dei Giacinti 2, 56128, Pisa, Calambrone, Italy

    Jacopo Baldacci, M. Grazia Alessandrì, Alessandra Tessa, Anna Rubegni, Renzo Guerrini & Filippo Maria Santorelli

  4. Neurogenetics Division, Clinics Hospital of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Charles Marques Lourenḉo

  5. Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy

    Alessandro Simonati

Authors
  1. Francesco Mari
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  2. Beatrice Berti
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  3. Alessandro Romano
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  4. Jacopo Baldacci
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  5. Riccardo Rizzi
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  6. M. Grazia Alessandrì
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  7. Alessandra Tessa
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  8. Elena Procopio
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  9. Anna Rubegni
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  10. Charles Marques Lourenḉo
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  11. Alessandro Simonati
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  12. Renzo Guerrini
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  13. Filippo Maria Santorelli
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Corresponding authors

Correspondence to Renzo Guerrini or Filippo Maria Santorelli.

Ethics declarations

This study was approved by the Tuscany Regional Pediatric Ethics committee. All the procedures complied with the Helsinki Declaration of 1975. Genetic studies were performed after parental written informed consent.

Conflict of interest

The authors declare that they have no conflict of interests.

Additional information

The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.

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Mari, F., Berti, B., Romano, A. et al. Clinical and neuroimaging features of autosomal recessive spastic paraplegia 35 (SPG35): case reports, new mutations, and brief literature review. Neurogenetics 19, 123–130 (2018). https://doi.org/10.1007/s10048-018-0538-8

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  • DOI: https://doi.org/10.1007/s10048-018-0538-8

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