Homozygous 4.1(-) hereditary elliptocytosis associated with a point mutation in the downstream initiation codon of protein 4.1 gene.
We studied a 43 yr-old Spanish patient with homozygous 4.1(-) hereditary elliptocytosis. Any form of protein 4.1 was missing in the red cells. Spectrin and actin were slightly, yet significantly, diminished. Alterations appeared at the level of proteins 4.5 and 4.9. Glycophorin C was sharply reduced. The abnormal allele was associated with the -++-- haplotype (Pvu II, Bgl II, Bgl II, Pvu II, Pvu II). mRNA 4.1(-) had an apparently normal size but was diminished by about two-thirds. Because the abnormal phenotype pertained to the red cell, we sequenced the 4.1 cDNA regions that appear critical to this cell type. The ultimate change turned out to be a point mutation of the downstream translation initiation codon (AUG-->AGG). No disorders in other cell types could be related with certainty to the present 4.1(-) HE allele.
Dalla Venezia
N
N
Centre National de la Recherche Scientifique Unité de Recherche Associée 1171, Faculté de Médecine Grange-Blanche, Lyon, France.
Gilsanz
F
F
Alloisio
N
N
Ducluzeau
M T
MT
Benz
E J
EJ
Delaunay
J
J
D000328:Adult; D001483:Base Sequence; D003062:Codon; D003598:Cytoskeletal Proteins; D004247:DNA / Q000737:chemistry; D004612:Elliptocytosis, Hereditary / Q000235:genetics*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D017354:Point Mutation; D012333:RNA, Messenger / Q000032:analysis
D003062:Codon; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D004247:DNA