RT Journal Article
SR Electronic
T1 Complicated spastic paraplegia in patients with <em>AP5Z1</em> mutations (SPG48)
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams &amp; Wilkins
SP e98
DO 10.1212/NXG.0000000000000098
VO 2
IS 5
A1 Hirst, Jennifer
A1 Madeo, Marianna
A1 Smets, Katrien
A1 Edgar, James R.
A1 Schols, Ludger
A1 Li, Jun
A1 Yarrow, Anna
A1 Deconinck, Tine
A1 Baets, Jonathan
A1 Van Aken, Elisabeth
A1 De Bleecker, Jan
A1 Datiles, Manuel B.
A1 Roda, Ricardo H.
A1 Liepert, Joachim
A1 Züchner, Stephan
A1 Mariotti, Caterina
A1 De Jonghe, Peter
A1 Blackstone, Craig
A1 Kruer, Michael C.
YR 2016
UL http://ng.neurology.org/content/2/5/e98.abstract
AB 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.HSP=hereditary spastic paraplegia; NCS=nerve conduction study; PAS=periodic acid-Schiff; PSP=progressive supranuclear palsy; SCA=spinocerebellar ataxia