The Spectrum of Somatic Mutations in thePIG-AGene 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-linkedPIG-Agene 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 thePIG-Agene and that the majority are frameshift mutations producing a non-functional PIG-A protein (PIG-Ao). In addition, we found 1 total deletion of thePIG-Agene, 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 missensePIG-Amutations should help elucidate structure-function relationships in the PIG-A protein.