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


Authors: Nafa, K.; Bessler, M.; Castro-Malaspina, H.; Jhanwar, S.; Luzzatto, L.
Article Title: The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal hemoglobinuria includes large deletions and small duplications
Abstract: 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°). 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.
Keywords: clinical article; human cell; somatic mutation; exon; frameshift mutation; gene deletion; missense mutation; mutation; sequence deletion; flow cytometry; polymerase chain reaction; phenotype; gene; protein; membrane proteins; structure activity relation; dna; gene duplication; x chromosome; hematopoietic stem cell; dna mutational analysis; nucleic acid hybridization; paroxysmal nocturnal hemoglobinuria; aplastic anemia; hemoglobinuria, paroxysmal; polyacrylamide gel electrophoresis; nucleotide; sequence analysis, dna; southern blotting; glycan; polymorphism, single-stranded conformational; heteroduplex; phosphatidylinositol; heteroduplex analysis; humans; human; male; female; priority journal; article; sus scrofa; single strand conformation analysis
Journal Title: Blood Cells, Molecules, and Diseases
Volume: 24
Issue: 3
ISSN: 1079-9796
Publisher: Elsevier Inc.  
Date Published: 1998-09-01
Start Page: 370
End Page: 384
Language: English
DOI: 10.1006/bcmd.1998.0203
PUBMED: 10087994
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Khedoudja Nafa
    185 Nafa
  2. Suresh C Jhanwar
    220 Jhanwar
  3. Lucio Luzzatto
    104 Luzzatto