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.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / chemistry
  • Antigens, CD / genetics*
  • Base Sequence
  • Cells, Cultured
  • DNA Mutational Analysis
  • Female
  • Fibroblasts / metabolism
  • Homocysteine / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / genetics*
  • Methylmalonic Acid / metabolism
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neonatal Screening / methods*
  • Pregnancy
  • Receptors, Cell Surface
  • Transcobalamins / metabolism*
  • Vitamin B 12 / metabolism*

Substances

  • Antigens, CD
  • CD320 protein, human
  • Receptors, Cell Surface
  • Transcobalamins
  • Homocysteine
  • Methylmalonic Acid
  • Vitamin B 12