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dc.contributor.authorHirst, Jennifer
dc.contributor.authorMadeo, Marianna
dc.contributor.authorSmets, Katrien
dc.contributor.authorEdgar, James
dc.contributor.authorSchols, Ludger
dc.contributor.authorLi, Jun
dc.contributor.authorYarrow, Anna
dc.contributor.authorDeconinck, Tine
dc.contributor.authorBaets, Jonathan
dc.contributor.authorVan Aken, Elisabeth
dc.contributor.authorDe Bleecker, Jan
dc.contributor.authorDatiles, Manuel B
dc.contributor.authorRoda, Ricardo H
dc.contributor.authorLiepert, Joachim
dc.contributor.authorZüchner, Stephan
dc.contributor.authorMariotti, Caterina
dc.contributor.authorDe Jonghe, Peter
dc.contributor.authorBlackstone, Craig
dc.contributor.authorKruer, Michael C
dc.date.accessioned2018-12-20T00:31:58Z
dc.date.available2018-12-20T00:31:58Z
dc.date.issued2016-10
dc.identifier.issn2376-7839
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287264
dc.description.abstractOBJECTIVE: 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.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleComplicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).
dc.typeArticle
prism.issueIdentifier5
prism.publicationDate2016
prism.publicationNameNeurol Genet
prism.startingPagee98
prism.volume2
dc.identifier.doi10.17863/CAM.34571
dcterms.dateAccepted2016-07-06
rioxxterms.versionofrecord10.1212/NXG.0000000000000098
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-10
dc.contributor.orcidHirst, Jennifer [0000-0001-9063-8494]
dc.contributor.orcidEdgar, James [0000-0001-7903-8199]
dc.identifier.eissn2376-7839
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (086598/Z/08/Z)
cam.issuedOnline2016-08-25


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International