The genetic abnormalities involving red cell membrane protein 4.1 with or without elliptocytosis

We have studied 20 caucasian individuals including 3 independent persons and 17 persons belonging to 6 unrelated families. These subjects are normal or elliptocytic. On biochemical grounds, families with hereditary elliptocytosis (HE) can be divided in two groups. (i) Three families in which HE is associated with a marked reduction (approximately 30%) of the band 4.1 percentage, upon scanning of SDS-polyacrylamide gels. This deficiency is associated with the absence of obvious clinical symptom and a dominant genetic transmission. (ii) Three HE families display a normal amount of band 4.1. Among two of them, HE is concomitant with moderate clinical manifestations and with a genetic transmission that seems to be morphologically recessive. In the last family, HE is transmitted as a dominant trait and is clinically silent. Finally, in the 3 isolated persons, HE is asymptomatic but the mode of genetic transmission could not be ascertained. One of them has a decreased amount of band 4.1 similar to that observed in the first group. To date, the band 4.1 deficiency is probably the best example of a relatively frequent specific molecular defect associated with a specific morphological abnormality. In one family with this type of HE, we have fortuitously discovered, at the heterozygous state, a variant of protein 4.1, shortened by about 8 500 daltons, involving both subcomponents 4.1a and 4.1b and morphologically silent.