We report on the complete absence of
protein 4.2 in two Tunisian siblings. The propositus presented with a
haemolytic anaemia that evolved in an intermittent fashion until she was cured by
splenectomy. Her red cells had a normal morphology, as well as normal deformability upon osmotic gradient ektacytometry. SDS-
polyacrylamide gel electrophoresis failed to reveal any
protein 4.2. Using anti-
protein 4.2 polyclonal
antibodies. Western blots were also unable to detect
protein 4.2. Preparation of inside out vesicles resulted in no detectable loss of
ankyrin. The propositus's sister presented with a
haemolytic anaemia but had not undergone
splenectomy; she showed the same biochemical features. The two cases presented of missing
protein 4.2 are the first ones to be described outside the Japanese population. Considered as homozygotes for some defect that must alter the
protein 4.2 gene itself, they exemplify a unique syndrome pertaining neither to elliptocytosis nor to spherocytosis, at least not closely. The parents, who are first cousins and whom we regarded as heterozygotes, were clinically and morphologically normal; they had a normal content of
protein 4.2. Therefore, the 4.2 (-)
haemolytic anaemia appears as entirely recessive.