Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type Journal Article
| Authors: | Nafa, K.; Mason, P. J.; Hillmen, P.; Luzzatto, L.; Bessler, M. |
| Article Title: | Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type |
| Abstract: | Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia associated with somatic mutations in the X-linked gene PIG-A, which encodes a protein involved in the biosynthesis of glycosyl phosphatidylinositol anchors. To further elucidate the molecular basis of paroxysmal nocturnal hemoglobinuria, we have worked out a systematic and relatively rapid methodology to scan for mutations in the entire coding region of the PIG-A gene. By this methodology, we have identified 15 different somatic mutations in 12 patients. The mutations were spread throughout the entire PIG-A-coding region. Of the mutations, 10 caused frameshifts, 6 caused small deletions, 3 caused small insertions, and 1 caused deletion-insertion. Five single base pair substitutions caused three missense mutations, one nonsense mutation, and one defect in the donor splice site of intron 4. In each of 3 patients, two independent mutations were identified. The predominance of frameshift mutations may reflect selection for somatic mutations giving rise to clones with a completely nonfunctional PIG-A protein |
| Keywords: | clinical article; controlled study; human cell; somatic mutation; frameshift mutation; sequence deletion; phenotype; membrane proteins; gene product; amino acid sequence; molecular sequence data; nucleotide sequence; hematopoietic cell; hemolytic anemia; base sequence; dna mutational analysis; point mutation; paroxysmal nocturnal hemoglobinuria; hemoglobinuria, paroxysmal; phosphatidylinositol; x chromosome linkage; human; male; female; priority journal; article; support, non-u.s. gov't; genes, structural |
| Journal Title: | Blood |
| Volume: | 86 |
| Issue: | 12 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1995-12-15 |
| Start Page: | 4650 |
| End Page: | 4655 |
| Language: | English |
| PUBMED: | 8541557 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V86.12.4650.bloodjournal86124650 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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