Pelizaeus-Merzbacher disease: Tight linkage to proteolipid protein gene exon variant

J. A. Trofatter, S. R. Dlouhy, W. DeMyer, P. M. Conneally, M. E. Hodes

Research output: Contribution to journalArticle

91 Scopus citations


Pelizaeus-Merzbacher disease (PMD) is a human X chromosome-linked dysmyelination disorder of the central nervous system for which the genetic defect has not yet been established. The jimpy mutation jp of the mouse is an X chromosome-linked disorder of myelin formation. The mutation is at an intron/exon splice site in the mouse gene for proteolipid protein (PLP). With the jimpy mouse mutation as a precedent, we focused our attention on the human PLP gene, which is found at Xq22. The polymerase chain reaction was used to amplify the exons of the PLP gene of an affected male from a large Indiana PMD kindred. DNA sequencing showed a C → T transition at nucleotide 40 of the second exon. An affected third cousin also showed this sequence variation, while two unaffected male relatives (sons of an obligate carrier female) had the normal cytidine nucleotide. Allele-specific oligonucleotides were used to generate data for linkage studies on the above mentioned PMD kindred. Our results show tight linkage (θ = 0) of PMD to PLP with a lod (logarithm of odds) score of 4.62. In six other unrelated PMD kindreds, only the normal-sequence oligonucleotide hybridized, which indicates genetic heterogeneity. The radical nature of the predicted amino acid change (proline to leucine), suggests that the PMD-causing defect may have been delineated in one kindred.

Original languageEnglish (US)
Pages (from-to)9427-9430
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Dec 22 1989


  • allele-specific oligonucleotide
  • linkage analysis
  • polymerase chain reaction
  • X chromosome

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Pelizaeus-Merzbacher disease: Tight linkage to proteolipid protein gene exon variant'. Together they form a unique fingerprint.

  • Cite this