title: Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2.
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.
  
  
  CONCLUSIONS
  This study confirms that mutations in SPTLC2 are associated with increased deoxySL formation causing HSANI.
authors: MRC Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors: Sinéad M
authors: SM
authors: Murphy
authors: Daniela
authors: D
authors: Ernst
authors: Yu
authors: Y
authors: Wei
authors: Matilde
authors: M
authors: Laurà
authors: Yo-Tsen
authors: YT
authors: Liu
authors: James
authors: J
authors: Polke
authors: Julian
authors: J
authors: Blake
authors: John
authors: J
authors: Winer
authors: Henry
authors: H
authors: Houlden
authors: Thorsten
authors: T
authors: Hornemann
authors: Mary M
authors: MM
authors: Reilly
mesh_terms: D000328:Adult; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000097:blood / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D051102:Serine C-Palmitoyltransferase / Q000235:genetics*; D013107:Sphingolipids / Q000097:blood*
chemical_list: D013107:Sphingolipids; C495089:SPTLC2 protein, human; D051102:Serine C-Palmitoyltransferase
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