Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter

is a rare congenital disease caused by defective fucosylation leading to immuno-deficiency and psychomotor retardation. We have previously identified the genetic defect of LAD II in a patient whose Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that renders this protein nonfunctional but correctly localized to the Golgi. We now report a novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient. We show that the truncation ren-ders this GFTP unable to localize to the Golgi, the compartment where it is re-quired. Furthermore, the missing part of the GFTP can be dissected into 2 regions, one that is needed for Golgi localization and one that is additionally required for the function of the GFTP. We investigated the subcellular localization of all known defective GFTPs allowing us to divide all genetically analyzed LAD II patients into 2 groups, one in which single amino acid exchanges in the GFTP impair its func-tion but not its subcellular localization, and another group with a dual defect in function and Golgi expression of the GFTP due to the absence of 2 important molecu-lar regions. (Blood. 2006;107:3959-3966) © 2006 by The American Society of Hematolog