COMPARISON OF THE ANKYRIN (AC)(N) MICROSATELLITES IN GENOMIC DNA AND MESSENGER-RNA REVEALS ABSENCE OF ONE ANKYRIN MESSENGER-RNA ALLELE IN 20-PERCENT OF PATIENTS WITH HEREDITARY SPHEROCYTOSIS

Combined deficiency of ankyrin and spectrin represents the most common biochemical abnormality in hereditary spherocytosis (HS). To examine whether a decrease in ankyrin mRNA represents a frequent cause of this type of HS, we took advantage of the reported (AC)(n) microsatellite polymorphism in the 3' untranslated region of ankyrin cDNA. We first measured the number of AC repeats in genomic DNA encoding erythrocyte ankyrin in 36 unrelated Czech HS patients with combined ankyrin and spectrin deficiency and found 21 of these subjects (58%) to be heterozygotes for the (AC)(n) microsatellite size. Further analysis of reticulocyte RNA showed that ankyrin cDNA from 7 of these 21 heterozygotes (33%) contained only one of the two ankyrin alleles, We conclude that approximately 1/3 of ankyrin-deficient autosomal dominant HS is caused by reduced expression of one ankyrin allele which, in turn, is caused by either a reduced transcription of one allele of the mutated ankyrin gene or abnormal processing or decreased stability of the mutant ankyrin mRNA, Because ankyrin deficiency is detected in approximate to 60% of HS subjects, this result suggests that approximate to 20% of all HS is caused by a decreased expression of one ankyrin mRNA allele. (C) 1995 by The American Society of Hematology.