This report describes spastic paraplegia 39 (SPG39), which is a subtype of spastic paraplegia. Familial SPG39 is inherited as an autosomal recessive. SPG39 is one of several neurological disorders caused by mutations in PNPLA6, which encodes a transmembrane protein that deacetylates intracellular phosphatidylcholine. See the report for neurodegenerative disease, PNPLA6-related (FBhh0000368) for information on experimental results using Drosophila models of this and related diseases.
[updated Aug. 2016 by FlyBase; FBrf0222196]
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]
[SPASTIC PARAPLEGIA 39, AUTOSOMAL RECESSIVE; SPG39](https://omim.org/entry/612020)
[PATATIN-LIKE PHOSPHOLIPASE DOMAIN-CONTAINING PROTEIN 6; PNPLA6](https://omim.org/entry/603197)
Spastic paraplegia 39 (SPG39) is associated with progressive distal upper and lower extremity wasting and spasticity; clinically variable in severity and with regard to other symptoms. In a study of several affected familiies, electrophysiologic studies were consistent with a motor axonopathy affecting upper and lower limbs. [from OMIM:612020; 2016.08.15]
PNPLA6 encodes a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. This protein is the target for neurodegeneration induced by certain organophosphorus compounds and chemical warfare agents. [Gene cards, PNPLA6; 2016.08.16]
Many to one (2 human to 1 Drosophila); the second orthologous gene in human is PNPLA7.