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Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12).

ABSTRACT: Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directed mutagenesis fully restored TCblR function.

SUBMITTER: Quadros EV

PROVIDER: S-EPMC2909035 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12).

Quadros Edward V EV Lai Shao-Chiang SC Nakayama Yasumi Y Sequeira Jeffrey M JM Hannibal Luciana L Wang Sihe S Jacobsen Donald W DW Fedosov Sergey S Wright Erica E Gallagher Renata C RC Anastasio Natascia N Watkins David D Rosenblatt David S DS

Human mutation 20100801 8

Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directe ...[more]

PMID: 20524213

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