Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2, hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network.
A novel mutation of 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene was detected in a 37-year-old Japanese patient with total lack of band 4.2 protein, designated as allele 4.2 Komatsu. In this patient, moderate uncompensated hemolytic anemia (red cell count 3.38 x 10(6)/microliters, hemoglobin 10.8 g/dl, hematocrit 30.9%, reticulocytes 12.4%, indirect bilirubin 1.84 mg/dl) with ovalostomatocytosis and increased osmotic fragility had been noted since birth. Family studies revealed no overt hemolytic anemia in other family members, essentially normal red cell morphology, and a normal profile of red cell membrane proteins including band 4.2. Genetic studies proved that the proband was homozygous and all the family members studied were heterozygous with respect to the mutation of 523 GAT-->TAT of the band 4.2 gene. Although band 4.2 was completely absent in the proband, trace amounts of 72 kDa and 74 kDa peptides were detected in the red cells of all the family members, in which the mutation of 424 GCT-->ACT at exon 3 of the band 4.2 gene (Nippon type) was not present. Electron microscopic studies with the surface replica method and the quick-freeze deep-etching method showed the most marked disorganization of the cytoskeletal network in the patient's red cells in situ among the cases of band 4.2 deficiencies we have studied. This suggests that the amino acid of the band 4.2 protein, which was affected by the present mutation in exon 4, is much more crucial for the functioning of band 4.2 protein than that at codon 142 in exon 3. The cytoplasmic domain of band 3 in the proband's red cells was essentially normal in protein chemistry and in gene analysis with single-stranded conformation polymorphism (SSCP).
Kanzaki
A
A
Department of Medicine, Kawasaki Medical School, Kurashiki City, Japan.
Yawata
Y
Y
Yawata
A
A
Inoue
T
T
Okamoto
N
N
Wada
H
H
Harano
T
T
Harano
K
K
Wilmotte
R
R
Hayette
S
S
D000328:Adult; D000483:Alleles; D000745:Anemia, Hemolytic, Congenital / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics*; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000648:ultrastructure*; D004913:Erythrocytes, Abnormal / Q000648:ultrastructure*; D005260:Female; D005613:Freeze Etching; D005796:Genes; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C044791:erythrocyte membrane band 4.2 protein