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Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

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Abstract
Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders.

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MLA
Hirst, Jennifer et al. “Complicated Spastic Paraplegia in Patients with AP5Z1 Mutations (SPG48).” NEUROLOGY-GENETICS 2.5 (2016): n. pag. Print.
APA
Hirst, J., Madeo, M., Smets, K., Edgar, J. R., Schols, L., Li, J., Yarrow, A., et al. (2016). Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48). NEUROLOGY-GENETICS, 2(5).
Chicago author-date
Hirst, Jennifer, Marianna Madeo, Katrien Smets, James R Edgar, Ludger Schols, Jun Li, Anna Yarrow, et al. 2016. “Complicated Spastic Paraplegia in Patients with AP5Z1 Mutations (SPG48).” Neurology-genetics 2 (5).
Chicago author-date (all authors)
Hirst, Jennifer, Marianna Madeo, Katrien Smets, James R Edgar, Ludger Schols, Jun Li, Anna Yarrow, Tine Deconinck, Jonathan Baets, Elisabeth Van Aken, Jan De Bleecker, Manuel B Datiles, Ricardo H Roda, Joachim Liepert, Stephan Züchner, Caterina Mariotti, Peter De Jonghe, Craig Blackstone, and Michael C Kruer. 2016. “Complicated Spastic Paraplegia in Patients with AP5Z1 Mutations (SPG48).” Neurology-genetics 2 (5).
Vancouver
1.
Hirst J, Madeo M, Smets K, Edgar JR, Schols L, Li J, et al. Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48). NEUROLOGY-GENETICS. 2016;2(5).
IEEE
[1]
J. Hirst et al., “Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48),” NEUROLOGY-GENETICS, vol. 2, no. 5, 2016.
@article{8507741,
  abstract     = {Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious.
Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1.
Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material.
Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders.},
  articleno    = {e98},
  author       = {Hirst, Jennifer and Madeo, Marianna and Smets, Katrien and Edgar, James R and Schols, Ludger and Li, Jun and Yarrow, Anna and Deconinck, Tine and Baets, Jonathan and Van Aken, Elisabeth and De Bleecker, Jan and Datiles, Manuel B and Roda, Ricardo H and Liepert, Joachim and Züchner, Stephan and Mariotti, Caterina and De Jonghe, Peter and Blackstone, Craig and Kruer, Michael C},
  issn         = {2376-7839},
  journal      = {NEUROLOGY-GENETICS},
  language     = {eng},
  number       = {5},
  pages        = {9},
  title        = {Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)},
  url          = {http://dx.doi.org/10.1212/nxg.0000000000000098},
  volume       = {2},
  year         = {2016},
}

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