title: Transcobalamin deficiency due to activation of an intra exonic cryptic splice site.
abstract: Transcobalamin (TC), a vitamin B12 (cobalamin, Cbl) binding protein in plasma, promotes the cellular uptake of the vitamin by receptor-mediated endocytosis. Inherited TC deficiency is an autosomal recessive disorder characterized by megaloblastic anaemia caused by cellular vitamin B12 depletion. It may be accompanied by neurological complications, including a delay in psychomotor and mental development. This report describes three sisters with inherited TC deficiency resulting from a splicing defect in the TC gene. A point mutation was identified in intron 3 splice site of the TC gene that activates a cryptic splice site in exon 3. The transcript generated has an in-frame deletion of 81 nucleotides and the resulting truncated protein is unstable and not secreted by the cells. Until now, genetic studies have been reported in only five patients with TC deficiency and the molecular defect was different in each of them, which gives evidence for a genetic heterogeneity of the disease.
authors: Laboratoire de Pathologie Cellulaire et Moléculaire en Nutrition, EMI-INSERM 0014, Faculté de Médecine de Nancy, Cedex, France. b.namour@chu-nancy.fr
authors: Fares
authors: F
authors: Namour
authors: Anne-Catherine
authors: AC
authors: Helfer
authors: Edward V
authors: EV
authors: Quadros
authors: Jean-Marc
authors: JM
authors: Alberto
authors: Ha M
authors: HM
authors: Bibi
authors: Lars
authors: L
authors: Orning
authors: David S
authors: DS
authors: Rosenblatt
authors: Guéant
authors: G
authors: Jean-Louis
mesh_terms: D000328:Adult; D000749:Anemia, Megaloblastic / Q000097:blood / Q000235:genetics*; D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010290:Parents; D017354:Point Mutation; D022821:RNA Splice Sites; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035781:Siblings; D014155:Transcobalamins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D014162:Transfection; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D022821:RNA Splice Sites; D014155:Transcobalamins; D014805:Vitamin B 12