Submitted January 20, 2006
Accepted February 26, 2006
The mutation rate in PIG-A is normal in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
David J Araten* and Lucio Luzzatto
Division of Hematology, NYU School of Medicine and the New York VA Medical Center, New York, NY, USA
Istituto Tuscano Tumori, Firenze, Italy
* Corresponding author; email: david.araten{at}nyumc.org.
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 two 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 (µ) in humans, in which PIG-A itself is used as a sentinel gene, we have found that in 5 patients with PNH µ ranged from 1.24 to 11.2 x 10-7, against a normal range of 2.4 - 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.
