Human Genetics

, Volume 97, Issue 1, pp 45–48

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

Authors

  • Anna Savoia
    • Servizio di Genetica Medica, I.R.C.C.S. Ospedale “Casa Sollievo della Sofferenza”
  • Leonarda Ianzano
    • Servizio di Genetica Medica, I.R.C.C.S. Ospedale “Casa Sollievo della Sofferenza”
  • Claudio Lunardi
    • Istituto di Clinica MedicaUniversità degli Studi di Verona
  • Giorgio De Sandre
    • Istituto di Clinica MedicaUniversità degli Studi di Verona
  • Mario Carotenuto
    • Divisione di EmatologiaI.R.C.C.S. Ospedale “Casa Sollievo della Sofferenza”
  • Pellegrino Musto
    • Divisione di EmatologiaI.R.C.C.S. Ospedale “Casa Sollievo della Sofferenza”
  • Leopoldo Zelante
    • Servizio di Genetica Medica, I.R.C.C.S. Ospedale “Casa Sollievo della Sofferenza”
Original Investigation

DOI: 10.1007/BF00218831

Cite this article as:
Savoia, A., Ianzano, L., Lunardi, C. et al. Hum Genet (1996) 97: 45. doi:10.1007/BF00218831

Abstract

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.

Copyright information

© Springer-Verlag 1996