Clincial and pathological study of distal motor neuropathy with N88S mutation in BSCL2

Neuropathology. 2009 Oct;29(5):543-7. doi: 10.1111/j.1440-1789.2009.01011.x. Epub 2009 Mar 23.


Seipinopathy is an autosomal dominant inherited distal motor neuropathy caused by Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene mutations. We describe a Chinese family with seipinopathy in which nine patients from four successive generations were involved. The onset of age was from 13 to 40 years. Among them six were distal hereditary motor neuropathy type II with predominant weakness of lower extremities, while one of them was accompanied by pyramidal signs. The other three women were distal hereditary motor neuropathy type V with predominant atrophy of hands. Electrophysiological results in one patient demonstrated reduction of amplitude of compound muscle action potentials. Sural nerve biopsy showed loss of large myelinated fibers and fiber regeneration. Gene analysis revealed a heterozygous 263A-->G mutation in BSCL2 gene resulting in amino acid substitutions in N88S. This report suggests that a different type of distal hereditary motor neuropathy could exist within one family carrying N88S mutations. The axonal degeneration of sensory nerves appeared also in the disease.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • China
  • Family
  • Female
  • GTP-Binding Protein gamma Subunits / genetics*
  • Hand / innervation
  • Hand / pathology
  • Humans
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / pathology*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology
  • Nerve Fibers, Myelinated / pathology
  • Nerve Fibers, Myelinated / ultrastructure
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Pedigree
  • Point Mutation
  • Polymorphism, Single Nucleotide*
  • Sensory Receptor Cells / pathology
  • Sural Nerve / pathology
  • Sural Nerve / ultrastructure


  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits