Primary progressive multiple sclerosis as a phenotype of a PLP1 gene mutation

Ann Neurol. 2005 Sep;58(3):470-3. doi: 10.1002/ana.20601.


We report a 49-year-old woman with a history of progressive gait disturbance, white matter disease, and cerebrospinal fluid immunoglobulin abnormalities who met criteria for primary progressive multiple sclerosis and whose son died at age 10 years of an unknown congenital neurodevelopmental disorder. Sequencing of the proteolipid protein 1 gene showed a novel mutation, Leu30Arg (c.89TG), in the mother and son. Pelizaeus-Merzbacher disease is the cause of death in the son and explains the mother's adult-onset neurological disorder. This case goes against dogma that mothers of severely affected sons are asymptomatic as adults and expands the differential diagnosis of primary progressive multiple sclerosis to include proteolipid protein 1 gene mutations.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Arginine / genetics
  • Brain / pathology
  • Child
  • DNA Mutational Analysis / methods
  • Female
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / genetics
  • Magnetic Resonance Imaging / methods
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / genetics*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Mutation*
  • Myelin Proteolipid Protein / genetics*
  • Pelizaeus-Merzbacher Disease / genetics
  • Phenotype*


  • Membrane Proteins
  • Myelin Proteolipid Protein
  • PLP1 protein, human
  • leucinal
  • Arginine
  • Leucine