Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria.

Abstract:

:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with multiple and varied clinical manifestations. The biochemical defect in PNH resides in the incomplete enzymatic assembly of glycosylphosphatidylinositol (GPI) anchors used for surface protein attachment. In all patients tested thus far, the defect is at the level of N-acetylglucosamine attachment to phosphatidylinositol (complementation class A defect). A human cDNA, Piga, that repairs cell lines with the class A defect has been recently cloned, making Piga a candidate gene for PNH. In the current study, using highly purified GPI-deficient granulocytes, we have performed Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of Piga in four patients with PNH. In each case, we have identified a mutation in the Piga coding sequence: three frameshift mutations were found, and a single nucleotide substitution (missense) mutation was identified. Our results provide convincing evidence that alterations in the Piga gene are responsible for PNH.

journal_name

Blood

journal_title

Blood

authors

Ware RE,Rosse WF,Howard TA

subject

Has Abstract

pub_date

1994-05-01 00:00:00

pages

2418-22

issue

9

eissn

0006-4971

issn

1528-0020

journal_volume

83

pub_type

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