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Martinez-Duncker, I ; Dupre, T ; Piller, V ; Piller, F ; Candelier, JJ ; Trichet, C ; Tchernia, G ; Oriol, R ; Mollicone, R

Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter

Blood 105 (7) 2671-2676

par Administrateur - publié le , mis à jour le

Abstract :

We have identified a homozygous G > A substitution in the donor splice site of intron 6 (IVS6 + 1G > A) of the cytidine monophosphate (CMP)-sialic acid transporter gene of Lec2 cells as the mutation responsible for their asialo phenotype. These cells were used in complementation studies to test the activity of the 2 CMP-sialic acid transporter cDNA alleles of a patient devoid of sialyl-Le(x) expression on polymorphonuclear cells. No complementation was obtained with either of the 2 patient alleles, whereas full restoration of the sialylated phenotype was obtained in the Lec2 cells transfected with the corresponding human wild-type transcript. The inactivation of one patient allele by a double microdeletion inducing a premature stop codon at position 327 and a splice mutation of the other allele inducing a 130-base pair (bp) deletion and a premature stop codon at position 684 are proposed to be the causal defects of this disease.