Pure or complex autosomal recessive spastic paraplegia
-Rare genetic disease
-Rare neurologic disease
Comment:
AP5Z1 forms a subunit of the adaptor protein complex 5 (AP-5), which is associated with the known ARHSP-associated proteins spatacsin (SPG11) and spastizin (SPG15). Mutations in AP5Z1, a gene playing a role in intracellular membrane trafficking, have been reported to be associated with spastic paraplegia type 48 (SPG48) (PMID:25333062).
Slabicki et al. (2010) reported 2 French sibs with progressive spastic paraplegia associated with urinary incontinence from ages 50 and 49 years, respectively. One had normal cerebral MRI, whereas the other had spinal hyperintensities in the cervical spine. ... Slabicki et al. (2010) reported 2 French sibs with progressive spastic paraplegia associated with urinary incontinence from ages 50 and 49 years, respectively. One had normal cerebral MRI, whereas the other had spinal hyperintensities in the cervical spine. The unaffected parents were not known to be consanguineous, but they originated from 2 neighboring villages.
By direct sequencing of the KIAA0415 gene in 166 unrelated patients with unexplained hereditary spastic paraplegia, Slabicki et al. (2010) identified a homozygous truncating mutation in 2 affected French sibs (613653.0001). Another patient with sporadic disease was heterozygous ... By direct sequencing of the KIAA0415 gene in 166 unrelated patients with unexplained hereditary spastic paraplegia, Slabicki et al. (2010) identified a homozygous truncating mutation in 2 affected French sibs (613653.0001). Another patient with sporadic disease was heterozygous for another truncating mutation (613653.0002), but a second mutation was not identified. Studies of lymphoblastoid cells derived from 1 patient showed increased sensitivity to DNA-damaging drugs. The findings suggested a link between this form of spastic paraplegia, which could be considered a neurodegenerative disease, and defects in DNA repair. Slabicki et al. (2010) studied KIAA0415 as a candidate gene in this disorder because of its role in a core protein complex with the other SPG-related genes SPG11 (610844) and SPG15 (ZFYVE26; 612012).