Uniquely higher incidence of isolated or combined deficiency of band 3 and/or band 4.2 as the pathogenesis of autosomal dominantly inherited hereditary spherocytosis in the Japanese population.
To clarify the pathogenesis of hereditary spherocytosis (HS), red cell membrane protein components were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 3.5-17% exponential gradient according to the method of Fairbanks et al. and of Laemmli in 47 HS cases from 32 unrelated Japanese families. The relative contents of each membrane protein fraction, which was stained by Coomassie blue, were expressed as their ratios to those of total membrane proteins. The density of each band of red cell membrane proteins in 47 HS patients was compared to that in 10 normal controls or in 4 high-reticulocyte controls. Various isolated or combined deficiencies of membrane proteins in these HS patients were detected by identifying the amounts of membrane proteins, which were > 1 S.D. (91%) or 2 S.D. (53%) of the mean values of normal controls, and > 1 S.D. (100%) or 2 S.D. (98%) of those of high-reticulocyte controls. Contrary to the commonly held belief that most of the autosomal dominantly-inherited HS demonstrate isolated or combined deficiency of ankyrin (ANK) and/or spectrin (SP), a much lower incidence of isolated or combined deficiency of SP and/or ANK was observed in these Japanese HS patients; 19% (> 1 S.D.) or 12% (2 S.D.) compared to normal controls, or 2% (1 S.D.) or 4% (2 S.D.) compared to high-reticulocyte controls. Instead, the incidence of isolated or combined deficiency of band 3 (B3) and/or band 4.2 (B4.2) was markedly elevated in these Japanese HS patients; 50% (1 S.D.) or 39% (2 S.D.) compared to normal controls, or 78% (1 S.D.) or 88% (2 S.D.) compared to high-reticulocyte controls. Other combined deficiencies were also observed, but the incidence was much lower. Therefore, distinct characteristics, i.e., higher incidence of isolated or combined deficiency of B4.2 and/or B3 with much lower incidence of ANK and/or SP deficiency, were observed in Japanese HS patients.
Inoue
T
T
Department of Medicine, Kawasaki Medical School, Kurashiki City, Japan.
Kanzaki
A
A
Yawata
A
A
Wada
H
H
Okamoto
N
N
Takahashi
M
M
Sugihara
T
T
Yamada
O
O
Yawata
Y
Y
D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency*; D017487:Ankyrins; D001798:Blood Proteins / Q000172:deficiency*; D003598:Cytoskeletal Proteins; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins; D013049:Spectrin / Q000172:deficiency; D013103:Spherocytosis, Hereditary / Q000209:etiology* / Q000235:genetics
D001457:Anion Exchange Protein 1, Erythrocyte; D017487:Ankyrins; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C044791:erythrocyte membrane band 4.2 protein; D013049:Spectrin