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GENATLAS PHENOTYPE
last update : 22-05-2010
Symbol HSAN1
Location 9q22.31
Name hereditary sensory and autonomic neuropathy, type 1
Other name(s) neuropathy, hereditary sensory radicular
Corresponding gene SPTLC1
Other symbol(s) HSN1
Main clinical features
  • sensorimotor axonal neuropathy with onset in the first or second decades of life
    • with perforating ulcers of the feet, shooting pains, and deafness, neuropathic arthropathy, recurrent ulceration of the lower extremities, and signs of radicular sensory deficiency in both the upper and the lower extremities without any motor dysfunction
  • sensory axonal neuropathy but in many individuals there was electrical evidence of demyelination
    • Genetic determination autosomal dominant
    Function/system disorder neurology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/gain of function G1160C, A387G severe phenotype
    missense   abnormal protein/loss of function C133Y or C133W resulting in a protein that can heterodimerize with SPTLC2
    missense   abnormal protein/gain of function gain of function mutation, which results in the formation of two atypical and neurotoxic sphingolipid metabolites (PMID: 20097765)
    Remark(s) . mutations induce a shift in the substrate specificity of serine palmitoyltransferase , which leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine (PMID: 20097765))
  • HSAN1 mutations perturb the active site of SPTLC1 resulting in a gain of function that is responsible for the HSAN1 phenotype (PMID: 20504773))