This report describes neuropathy, hereditary sensory and autonomic, type IC (HSAN1C), which exhibits autosomal dominant inheritance. The human gene implicated in this disease is serine palmitoyltransferase 2 (SPTLC2), which is a key enzyme in sphingolipid biosynthesis. There is a single orthologous gene in Drosophila, lace, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\lace is also orthologous to SPTLC3.
The human SPTLC2 gene has not been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\lace typically die during the embryonic stage. In an RNAi screen for genes with essential function in glia, lace was identified and was found to be specifically required for the process of uniform ensheathment of axons by the glia. Neural-specific knockdown does not result in visible alterations of axonal morphology. RNAi experiments targeting other Drosophila genes involved in the biosynthesis of ceramide phosphoethanolamine produce similar results.
The serine palmitoyltransferase subunit SPTLC1 is also implicated in a subtype of hereditary sensory and autonomic neuropathy; see the human disease model report 'neuropathy, hereditary sensory and autonomic, type IA' (FBhh0000473).
[updated May 2019 by FlyBase; FBrf0222196]
Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system that predominantly affect the sensory and autonomic neurons (Auer-Grumbach, 2013; pubmed:23931820).
Hereditary sensory and autonomic neuropathies (HSANs) occur much less frequently than do the primary hereditary motor sensory neuropathies (HMSNs) (http://www.uptodate.com/contents/hereditary-sensory-and-autonomic-neuropathies).
The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN), are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction, typically characterized by characterized by insensitivity to pain and resulting in injury to the fingers, tongue, lips, and other distal appendages. [from MIM:162400, MIM:616488; 2017.07.10]
[NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IC; HSAN1C](https://omim.org/entry/613640)
[SERINE PALMITOYLTRANSFERASE, LONG-CHAIN BASE SUBUNIT 2; SPTLC2](https://omim.org/entry/605713)
Hereditary sensory and autonomic neuropathy type IC (HSAN1C) is caused by heterozygous mutation in the SPTLC2 gene. [from MIM:613640; 2019.05.06]
SPTLC2 encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is a key enzyme in sphingolipid biosynthesis. [from Gene Cards, SPTLC2; 2019.05.06]
Many to one: 2 human to 1 Drosophila. The second human gene is SPTLC3.
High-scoring ortholog of human SPTLC2; moderate-scoring ortholog of SPTLC3 (1 Drosophila to 2 human). Dmel\lace shares 57% identity and 77% similarity with SPTLC2.
