Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B12
✍ Scribed by Edward V. Quadros; Shao-Chiang Lai; Yasumi Nakayama; Jeffrey M. Sequeira; Luciana Hannibal; Sihe Wang; Donald W. Jacobsen; Sergey Fedosov; Erica Wright; Renata C. Gallagher; Natascia Anastasio; David Watkins; David S. Rosenblatt
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 290 KB
- Volume
- 31
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
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 sitedirected mutagenesis fully restored TCblR function.