This report describes spastic paraplegia, SPTSSA-related, a complex type of hereditary spastic paraplegia. The human gene implicated is SPTSSA, which encodes serine palmitoyltransferase small subunit A, a component of serine palmitoyltransferase (SPT) which catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. There are two moderate-scoring fly orthologs, Dmel\CG34293 and Dmel\CG34194; neither gene has been analyzed in the context of this disease model.
A wild-type construct of the human Hsap\SPTSSA gene has been introduced into flies. Additionally, a single-chain construct of serine palmitoyltransferase including all SPT subunits ('scSPT'), both wild-type and with SPTSSA variants implicated in disease (T51I and H59L) have been introduced into flies. See the 'Disease-Implicated Variants' table below. Ubiquitous overexpression of wild-type or variant scSPT causes excessive biosynthesis of sphingolipids, resulting in severe neurological defects and shortened lifespan.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[SPASTIC PARAPLEGIA 90A, AUTOSOMAL DOMINANT; SPG90A](https://omim.org/entry/620416)
[SERINE PALMITOYLTRANSFERASE, SMALL SUBUNIT, A; SPTSSA](https://omim.org/entry/613540)
Autosomal dominant spastic paraplegia-90A (SPG90A) is characterized by motor impairment and progressive lower extremity spasticity as well as neurologic findings, cognitive impairment, and hearing loss (Srivastava, et al., 2023, pubmed:36718090; FBrf0256324). [from MIM:620416; 2023.07.11]
Autosomal dominant spastic paraplegia-90A (SPG90A) is caused by heterozygous mutation in the SPTSSA gene on chromosome 14q13. Biallelic mutation in the SPTSSA gene causes autosomal recessive SPG90B (MIM:620417). [from MIM:620416; 2023.07.11]
SPTSSA variants impaired ORMDL regulation and caused excessive sphingolipid synthesis (Srivastava, et al., 2023, pubmed:36718090; FBrf0256324).
Serine palmitoyltransferase catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTA is a small SPT subunit that stimulates SPT activity and confers acyl-CoA preference to the SPT catalytic heterodimer of SPTLC1 and either SPTLC2 or SPTLC3 (Han et al., 2009, pubmed:19416851). [from MIM:613540; 2023.07.11]
Moderate-scoring ortholog of human SPTSSA and SPTSSB (2 Drosophila to 2 human).
Moderate-scoring ortholog of human SPTSSA and SPTSSB (2 Drosophila to 2 human).
