The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications

Blood Cells Mol Dis. 1998 Sep;24(3):370-84. doi: 10.1006/bcmd.1998.0203.


Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder characterized by chronic hemolysis with hemoglobinuria and venous thrombosis. PNH clones arise through somatic mutations in the X-linked PIG-A gene that occur in early hematopoietic stem cells. Here we report 28 previously undescribed mutations; we confirm that somatic mutations are spread throughout the entire coding region of the PIG-A gene and that the majority are frameshift mutations producing a non-functional PIG-A protein (PIG-A(o)). In addition, we found 1 total deletion of the PIG-A gene, and 2 short nucleotide duplications. Although mutations are spread throughout the entire coding region, we observe more missense mutations in exon 2 than in the other exons. The increasing number of identified missense PIG-A mutations should help elucidate structure-function relationships in the PIG-A protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Gene Duplication*
  • Hemoglobinuria, Paroxysmal / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Nucleic Acid Hybridization
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA
  • Sequence Deletion*
  • X Chromosome / genetics*


  • Membrane Proteins
  • phosphatidylinositol glycan-class A protein