ClinVar

Brennan et al. (1986) described a 25-year-old man with congenital hemolytic anemia who was found to have the mutation of Hb Atlanta (beta75 leu-to-pro) and that of Hb Coventry (beta141 leu deleted) in the same beta-globin chain along with a normal beta-globin chain and a beta-globin chain with only the Hb Atlanta mutation. They stated that this is the sixth known example of 2 changes in 1 beta chain. They postulated that the doubly abnormal beta-globin was a beta-delta globin originating by a Lepore-type-mechanism. Brennan et al. (1992) found on restudy that leu141 was in fact not deleted but replaced by a novel amino acid which they suggested was hydroxyleucine; they proposed that the change resulted from posttranslational oxidation of leu141 as a consequence of perturbation of the haem environment caused by the leu75-to-pro mutation. The finding was consistent with the report of George et al. (1992) who found no evidence of deletion of leu141 in genomic DNA. The heterozygous patients have 3 hemoglobins: HbA, Hb Atlanta, and Hb Atlanta-Coventry. The last 2 are the products of a single gene. A similar situation obtains with Hb Vicksburg (141900.0293), in which deletion of leu75 is not coded for in genomic DNA. Coleman et al. (1988) posited somatic mutation in that instance; however, a mechanism similar to that with Hb Atlanta-Coventry is possible.