Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients

Hum Genet. 1996 Jan;97(1):45-8. doi: 10.1007/BF00218831.


Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface proteins resulting from a defect in one step of GPI-anchor biosynthesis. Recent analysis has shown that mutations at the PIG-A (phosphatidylinositoglycan-class A) gene are responsible for GPI-anchor deficiency in all PNH patients. In the current study, we describe three new mutations of the PIG-A gene in Italian patients with PNH. The analysis has been performed by RNA/single-strand conformation polymorphism using genomic DNA purified from nucleated peripheral blood cells. An abnormal pattern of migration of polymerase chain reaction amplified fragments containing exons 2 and 5 was observed. Sequencing analysis led to the identification of three mutations: a transversion C-to-A creating a stop codon (Y98X), an A insertion at position 460 (460insA), and a C deletion (1114delC). All the mutations cause a premature termination of the translation of the PIG-A protein.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Codon
  • DNA / blood
  • DNA Primers
  • Erythrocytes / metabolism
  • Exons
  • Glycosylphosphatidylinositols / biosynthesis
  • Glycosylphosphatidylinositols / genetics*
  • Hemoglobinuria, Paroxysmal / genetics*
  • Humans
  • Italy
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Point Mutation
  • Polymerase Chain Reaction
  • Sequence Deletion


  • Codon
  • DNA Primers
  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • phosphatidylinositol glycan-class A protein
  • DNA