Genotypic and phenotypic analyses of proten 4.2 anomalies *
Anomalies of red cell membrane protein 4.2 (P4.2) have been considered in the possible pathogenesis of congenital hemolytic anemias. These P4.2 anomalies have been discovered almost exclusively in the Japanese population. In this study, the P4.2 anomalies which were found in patients with congenital hemolytic anemias were based on the results of protein chemistry and gene analysis. The P4.2 anomalies were identified by quantitative membrane protein analysis from 179 patients in 80 kindreds with congenital hemolytic anemias. Regarding P4.2 anomalies, patients with hereditary spherocytosis of non-autosomal dominant inheritance, P4.2 complete deficiencies, and P4.2 doublet Nagano were detected. These cases were divided into two type ; i.e., (1) a qualitative anomaly (P4-2 doublet Nagano), and (2) a quantitaiive anomaly. The latter was further classified into three subgroups ; i.e., (a) complete deficiency, (b) moderate～severe deficiency, and (c) mild deficiency. To elucidate the pathogenesis of these disorders, gene analyses were carried out on the P4.2 gene and the band 3 gene in 25 patients with P42 ano-malies. In the qualitative P4.2 anomaly, a point mutation (R488H) was identified on the P4.2 gene in P4.2 doublet Nagano, in which abnormal proteins (72/74kD) were detected by protein chemis-try. In the quantitative P4.2 anomalies, mutant genes were detected ; i.e., (1) Band 3 Fukuoka (G130R) in the patients with moderate to severe P4.2 deficiency, and (2) a P4.2 mutation of the Nippon type (A142T) in patients with complete P4.2 deficiency. No mutations were detected in patients with mild isolated deficiency of P4.2. Therefore, it was concluded that P4.2 abnormalities were derived from qualitative and quantitative anomalies detected by protein chcmistry and molecular biology, (Accepted on October 27, 1998) Kawasaki Igakkaishi 24(4) : 243-260. 1998
