Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12).
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.
Quadros
Edward V
EV
Department of Medicine, SUNY-Downstate Medical Center, Brooklyn, New York 11203, USA. Edward.Quadros@downstate.edu
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
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D008764:Methylmalonic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening / Q000379:methods*; D011247:Pregnancy; D011956:Receptors, Cell Surface; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism*
D015703:Antigens, CD; C538894:CD320 protein, human; D011956:Receptors, Cell Surface; D014155:Transcobalamins; D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12