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

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.