Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).
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Authors
Madeo, Marianna
Smets, Katrien
Edgar, James R
Schols, Ludger
Li, Jun
Yarrow, Anna
Deconinck, Tine
Baets, Jonathan
Van Aken, Elisabeth
De Bleecker, Jan
Datiles, Manuel B
Roda, Ricardo H
Liepert, Joachim
Züchner, Stephan
Mariotti, Caterina
De Jonghe, Peter
Blackstone, Craig
Kruer, Michael C
Publication Date
2016-10Journal Title
Neurol Genet
ISSN
2376-7839
Publisher
Ovid Technologies (Wolters Kluwer Health)
Volume
2
Issue
5
Pages
e98
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
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).. Neurol Genet, 2 (5), e98. https://doi.org/10.1212/NXG.0000000000000098
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.
Sponsorship
Wellcome Trust (086598/Z/08/Z)
Identifiers
External DOI: https://doi.org/10.1212/NXG.0000000000000098
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287264
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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