A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT.

Abstract:

:To ascertain the genetic basis of a paroxysmal nocturnal hemoglobinuria (PNH) case without somatic mutations in PIGA, we performed deep next-generation sequencing on all exons of known genes of the glycosylphosphatidylinositol (GPI) anchor synthesis pathway. We identified a heterozygous germline splice site mutation in PIGT and a somatic 8-MB deletion in granulocytes affecting the other copy of PIGT. PIGA is essential for GPI anchor synthesis, whereas PIGT is essential for attachment of the preassembled GPI anchor to proteins. Although a single mutation event in the X-chromosomal gene PIGA is known to cause GPI-anchored protein deficiency, 2 such hits are required in the autosomal gene PIGT. Our data indicate that PNH can occur even in the presence of fully assembled GPI if its transfer to proteins is defective in hematopoietic stem cells.

journal_name

Blood

journal_title

Blood

authors

Krawitz PM,Höchsmann B,Murakami Y,Teubner B,Krüger U,Klopocki E,Neitzel H,Hoellein A,Schneider C,Parkhomchuk D,Hecht J,Robinson PN,Mundlos S,Kinoshita T,Schrezenmeier H

doi

10.1182/blood-2013-01-481499

subject

Has Abstract

pub_date

2013-08-15 00:00:00

pages

1312-5

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2013-01-481499

journal_volume

122

pub_type

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