The β0‐thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence

Abstract

An AG dinucleotide is an invariant feature of all acceptor splice sites, and deletion or substitution of (one of) these nucleotides will result in abnormal processing of the β‐globin mRNA. Restriction endonuclease mapping of DNA from an American black patient with Hb S‐β⁰‐thalassemia failed to detect any deletion in the β⁰‐globin gene region, but cloning and sequencing of the β⁰‐globin gene showed a point mutation (A → C) in the highly conserved dinucleotide AG of the acceptor splice junction of the IVS‐2. Blot hybridization analysis of RNA prepared from the erythroid cells of the patient showed only RNA of normal size. The patient and her daughter, who has the same condition, have high levels of Hb F (27%–35%); the mechanism responsible for the greatly increased γ chain production remains unclear.