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Blood. 2013 Aug 15;122(7):1312-5. doi: 10.1182/blood-2013-01-481499. Epub 2013 Jun 3.

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

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Institute for Medical Genetics and Human Genetics, Charité Universitätsmedizin, Berlin, Germany.


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.

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