Open Close
General Information
Name
spastic paraplegia 78
FlyBase ID
FBhh0000988
Disease Ontology Term
Parent Disease
Overview

This report describes spastic paraplegia 78 (SPG78), which is a subtype of spastic paraplegia; SPG78 exhibits autosomal recessive inheritance. The human gene implicated in this disease, ATP13A2, is also implicated in a second neurodegenerative disease with some overlapping phenotypes, Kufor-Rakeb syndrome, aka Parkinson disease 9 (OMIM:606693, FBhh0000987). See the report for neurodegenerative disorders, ATP13A2-related (FBhh0000989) for information on experimental results using Drosophila models of this and related diseases.

[updated Mar. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: spastic paraplegia
Symptoms and phenotype

The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from OMIM:182600; 15.06.29]

Specific Disease Summary: spastic paraplegia 78
OMIM report

[SPASTIC PARAPLEGIA 78, AUTOSOMAL RECESSIVE; SPG78](https://omim.org/entry/617225)

Human gene(s) implicated

[ATPase 13A2; ATP13A2](https://omim.org/entry/610513)

Symptoms and phenotype

Autosomal recessive spastic paraplegia-78 is an adult-onset neurodegenerative disorder characterized predominantly by spasticity and muscle weakness of the lower limbs, resulting in gait difficulties and loss of ambulation in some patients. Affected individuals also have cerebellar signs, such as dysarthria, oculomotor disturbances, and limb and gait ataxia; brain imaging shows cerebellar atrophy. Some patients may have mild cognitive impairment or frank dementia. The phenotype is highly variable (summary by Estrada-Cuzcano et al., 2017; pubmed:28137957). [from OMIM:617225; 2019.03.19]

Genetics

Autosomal recessive spastic paraplegia 78 (SPG78) is caused by homozygous or compound heterozygous mutation in the ATP13A2. [from OMIM:617225; 2019.03.19]

Cellular phenotype and pathology
Molecular information

ATP13A2 encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. The encoded ATPase plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity; it is required for a proper lysosomal and mitochondrial maintenance. [Gene Cards, ATP13A2; 2019.03.19]

ATP13A2 encodes a lysosomal transmembrane P5B-type ATPase. ATP13A2 loss leads to lysosomal abnormalities, impaired mitochondrial function, increased metal sensitivity, and increased sensitivity to ER stress. It has been tied to autophagy and other cellular features of neurodegeneration (FBrf0241154 and references cited therein).

External links
Disease synonyms
autosomal recessive spastic paraplegia 78
SPG78
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (0)
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (0 groups)
        Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (2)