HB FANNIN-LUBBOCK IN 5 SPANISH FAMILIES IS CHARACTERIZED BY 2 MUTATIONS - BETA-111-GTC-]CTC-(VAL-]LEU) AND BETA-119-GGC-]GAC-(GLY-]ASP)

We have sequenced the amplified beta-globin genes of five, apparently unrelated, Spanish adults with a fast-moving hemoglobin variant, and o bserved a G (G) under bar C->G (A) under bar C mutation at codon 119 w hich identified the abnormality as Hb Fannin-Lubbock or alpha(2) beta( 2)119(GH2)Gly->Asp. In addition, we found a (G) under bar TC->(C) unde r bar TC change at codon 111 which leads to a Val->Leu replacement at this location. Protein analysis of the beta(A) and beta(X) chains from one of these individuals confirmed that both mutations are located on the same chromosome. It is hypothesized that some other known variant s may carry an additional mutation in one of their exons, resulting in a silent amino acid substitution which may have an effect on some phy sicochemical property. In the case of Hb Fannin-Lubbock, it appears li kely that the Val->Leu replacement at beta 111, rather than the Gly->A sp replacement of beta 119, is the cause of the instability of the var iant. The Hb Fannin-Lubbock variant in these Spanish families had a no rmal oxygen affinity.