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

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

  • Hum Mutat. 2010 Aug;31(8):924-9. doi: 10.1002/humu.21297.
Edward V Quadros 1,  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
Affiliations

Affiliation

  • 1 Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, New York 11203, USA. [email protected]
PMID: 20524213 DOI: 10.1002/humu.21297
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.

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