Hb Fannin-Lubbock in Five Spanish Families is Characterized by two Mutations: β111 GTC->CTC (VAL->LEU) AND β119 GGC->GAC (GLY->ASP)

Abstract

We have sequenced the amplified β-globin genes of five, apparently unrelated, Spanish adults with a fast-moving hemoglobin variant, and observed a GGC->GAC mutation at codon 119 which identified the abnormality as Hb Fannin-Lubbock or α₂β₂119(GH2)Gly->Asp. In addition, we found a GTC->CTC change at codon 111 which leads to a Val->Leu replacement at this location. Protein analysis of the β^A and β^X chains from one of these individuals confirmed that both mutations are located on the same chromosome. It is hypothesized that some other known variants may carry an additional mutation in one of their exons, resulting in a silent amino acid substitution which may have an effect on some physicochemical property. In the case of Hb Fannin-Lubbock, it appears likely that the Val->Leu replacement at β111, rather than the Gly->Asp replacement of β119, is the cause of the instability of the variant. The Hb Fannin-Lubbock variant in these Spanish families had a normal oxygen affinity.