Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).

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 stor

SUBMITTER: Hirst J 

PROVIDER: S-EPMC5001803 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature