A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216).
A novel spectrin variant carrying a truncated beta-chain and designated Spectrin Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the alpha I 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened beta-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta 220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.
Kanzaki
A
A
Department of Medicine, Kawasaki Medical School, Kurashiki, Japan.
Rabodonirina
M
M
Yawata
Y
Y
Wilmotte
R
R
Wada
H
H
Ata
K
K
Yamada
O
O
Akatsuka
J
J
Iyori
H
H
Horiguchi
M
M
D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000737:chemistry; D004612:Elliptocytosis, Hereditary / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D013049:Spectrin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D003062:Codon; D046911:Macromolecular Substances; D010446:Peptide Fragments; C077398:Spectrin Tokyo; D013049:Spectrin; D004247:DNA; D014357:Trypsin