Ontology highlight
ABSTRACT: Objective
To describe the clinical and neurophysiologic phenotype of a family with hereditary sensory and autonomic neuropathy type 1 (HSANI) due to a novel mutation in SPTLC2 and to characterize the biochemical properties of this mutation.Methods
We screened 107 patients with HSAN who were negative for other genetic causes for mutations in SPTLC2. The biochemical properties of a new mutation were characterized in cell-free and cell-based activity assays.Results
A novel mutation (A182P) was found in 2 subjects of a single family. The phenotype of the 2 subjects was an ulcero-mutilating sensory-predominant neuropathy as described previously for patients with HSANI, but with prominent motor involvement and earlier disease onset in the first decade of life. Affected patients had elevated levels of plasma 1-deoxysphingolipids (1-deoxySLs). Biochemically, the A182P mutation was associated with a reduced canonical activity but an increased alternative activity with alanine, which results in largely increased 1-deoxySL levels, supporting their pathogenicity.Conclusion
This study confirms that mutations in SPTLC2 are associated with increased deoxySL formation causing HSANI.
SUBMITTER: Murphy SM
PROVIDER: S-EPMC3716354 | biostudies-literature | 2013 Jun
REPOSITORIES: biostudies-literature
Murphy Sinéad M SM Ernst Daniela D Wei Yu Y Laurà Matilde M Liu Yo-Tsen YT Polke James J Blake Julian J Winer John J Houlden Henry H Hornemann Thorsten T Reilly Mary M MM
Neurology 20130508 23
<h4>Objective</h4>To describe the clinical and neurophysiologic phenotype of a family with hereditary sensory and autonomic neuropathy type 1 (HSANI) due to a novel mutation in SPTLC2 and to characterize the biochemical properties of this mutation.<h4>Methods</h4>We screened 107 patients with HSAN who were negative for other genetic causes for mutations in SPTLC2. The biochemical properties of a new mutation were characterized in cell-free and cell-based activity assays.<h4>Results</h4>A novel m ...[more]