This report describes spastic paraplegia 3A (SPG3A), which is a subtype of spastic paraplegia; it is an autosomal dominant form of the disease. The human gene implicated in this disease is Atlastin-1 (ATL1), which encodes a dynamin-related GTPase that plays a role in formation of the tubular endoplasmic reticulum (ER) network and in axon elongation in neurons. There is a single fly ortholog, atl, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\atl is orthologous to three other genes in human, ATL2, ATL3, and RNF112. The human ATL1 gene is also implicated in a form of hereditary sensory neuropathy (OMIM:613708).
The human ATL1 gene has not been introduced into flies.
Animals homozygous for a loss-of-function mutation of Dmel\atl die in late pupal stages; larva exhibit defects in neuroanatomy and neurophysiology. In homozygous third instar larvae, ER fragmentation is observed in motor neuron nerve terminals. Physical and genetic interactions have been described for atl; see below and in the gene report for atl.
[updated Sep. 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 3, AUTOSOMAL DOMINANT; SPG3A](https://omim.org/entry/182600)
[ATLASTIN GTPase 1; ATL1](https://omim.org/entry/606439)
This subtype of hereditary spastic paraplegia is associated with lower limb weakness and spasticity that is generally slowly progressive. HSP3A usually develops in early childhood with more than 80% of affected individuals developing spastic gait before 10 years of age. Later-onset cases are associated with more slowly progressive disease. Some individuals may develop urinary bladder hyperactivity, axonal neuropathy and/or distal muscle wasting. [from NORD: Hereditary Spastic Paraplegia; 2016.09.02]