Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria

Lancet. 1994 Apr 16;343(8903):951-3. doi: 10.1016/s0140-6736(94)90068-x.


Patients with paroxysmal nocturnal haemoglobinuria (PNH) have in their blood two red-cell populations, one normal and one deficient in proteins anchored to the membrane through a glycan phosphatidylinositol (GPI) structure. The PNH abnormality is due to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor biosynthesis. We show that in two patients, two PNH clones with different mutations co-exist, and must therefore have arisen independently. This finding supports the concept that PNH develops under the pressures of a positive selection mechanism whereby GPI-anchor-deficient haemopoietic cells have a survival advantage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Clone Cells
  • Glycosylphosphatidylinositols / deficiency
  • Hemoglobinuria, Paroxysmal / genetics*
  • Hemoglobinuria, Paroxysmal / physiopathology
  • Humans
  • Mutation
  • Polymerase Chain Reaction
  • Stem Cells / metabolism


  • Glycosylphosphatidylinositols