The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the presence in the patient's hematopoietic system of a large cell population with a mutation in the X-linked PIG-A gene. Although this abnormal cell population is often found to be monoclonal, it is not unusual that 2 or even several PIG-A mutant clones coexist in the same patient. Therefore, it has been suggested that the PIG-A gene may be hypermutable in PNH. By a method we have recently developed for measuring the intrinsic rate of somatic mutations (mu) in humans, in which PIG-A itself is used as a sentinel gene, we have found that in 5 patients with PNH, mu ranged from 1.24 x 10(-7) to 11.2 x 10(-7), against a normal range of 2.4 x 10(-7) to 29.6 x 10(-7) mutations per cell division. We conclude that genetic instability of the PIG-A gene is not a factor in the pathogenesis of PNH.
Division of Hematology, New York University School of Medicine and the New York Veterans Administration Medical Center, 10016, USA. david.araten@nyumc.org
David J
DJ
Araten
Lucio
L
Luzzatto
D000328:Adult; D000368:Aged; D002999:Clone Cells; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation
D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein