2 DISTINCT TRUNCATED VARIANTS OF ANKYRIN ASSOCIATED WITH HEREDITARY SPHEROCYTOSIS

We present two distinct truncated variants of ankyrin associated with mild to moderate hereditary spherocytosis, Ankyrin Saint-Etienne 1 was manifested by an additional band located between bands 2.1 and 2.2. I t was associated with a nonsense mutation in exon 39: TGG-->TGA; W1721 X. Ankyrin Saint-Etienne 2 appeared as two faint bands underlining ban ds 2.1 and 2.2. It was associated with a nonsense mutation in exon 41: CGA-->TGA; R1833X. Overall ankyrin was diminished in splenectomized p atients. Messenger RNAs Saint-Etienne 1 and 2 amounted to 20 and 37% o f the total ankyrin mRNA, respectively. Ankyrin molecules truncated in their C-terminal region retain some ability to bind to the membrane w hereas the bulk of nonsense mutations, located in more upstream region s, result in the mere disappearance of one haploid set of ankyrin, In the present cases, it was not possible to apportion the roles of ankyr in reduction and truncation in the pathogenesis of hereditary spherocy tosis. (C) 1998 Wiley-Liss, Inc.