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): 2671-6, 2005 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-15576474
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. A 4-base insertion in intron 6 was found in the mother and is proposed to be responsible for the splice mutation. We conclude that this defect is a new type of congenital disorder of glycosylation (CDG) of type IIf affecting the transport of CMP-sialic acid into the Golgi apparatus.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido N-Acetilneuramínico
/
Citidina Monofosfato
/
Proteínas de Transporte de Nucleótidos
/
Aparato de Golgi
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia